Alagille Syndrome: A multisystem disorder that is characterized by aplasia of intrahepatic bile ducts (BILE DUCTS, INTRAHEPATIC), and malformations in the cardiovascular system, the eyes, the vertebral column, and the facies. Major clinical features include JAUNDICE, and congenital heart disease with peripheral PULMONARY STENOSIS. Alagille syndrome may result from heterogeneous gene mutations, including mutations in JAG1 on CHROMOSOME 20 (Type 1) and NOTCH2 on CHROMOSOME 1 (Type 2).Receptor, Notch2: A notch receptor that plays an important role in CELL DIFFERENTIATION in a variety of cell types. It is the preferentially expressed notch receptor in mature B-LYMPHOCYTES.Chromosomes, Human, Pair 20: A specific pair of GROUP F CHROMOSOMES of the human chromosome classification.Calcium-Binding Proteins: Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.Intercellular Signaling Peptides and Proteins: Regulatory proteins and peptides that are signaling molecules involved in the process of PARACRINE COMMUNICATION. They are generally considered factors that are expressed by one cell and are responded to by receptors on another nearby cell. They are distinguished from HORMONES in that their actions are local rather than distal.Facies: The appearance of the face that is often characteristic of a disease or pathological condition, as the elfin facies of WILLIAMS SYNDROME or the mongoloid facies of DOWN SYNDROME. (Random House Unabridged Dictionary, 2d ed)Receptors, Notch: A family of conserved cell surface receptors that contain EPIDERMAL GROWTH FACTOR repeats in their extracellular domain and ANKYRIN repeats in their cytoplasmic domains. The cytoplasmic domain of notch receptors is released upon ligand binding and translocates to the CELL NUCLEUS where it acts as transcription factor.Syndrome: A characteristic symptom complex.Cholestasis: Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS).Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Bile Ducts: The channels that collect and transport the bile secretion from the BILE CANALICULI, the smallest branch of the BILIARY TRACT in the LIVER, through the bile ductules, the bile ducts out the liver, and to the GALLBLADDER for storage.Cholestasis, Intrahepatic: Impairment of bile flow due to injury to the HEPATOCYTES; BILE CANALICULI; or the intrahepatic bile ducts (BILE DUCTS, INTRAHEPATIC).Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another.Liver Diseases: Pathological processes of the LIVER.Liver Cirrhosis, Biliary: FIBROSIS of the hepatic parenchyma due to obstruction of BILE flow (CHOLESTASIS) in the intrahepatic or extrahepatic bile ducts (BILE DUCTS, INTRAHEPATIC; BILE DUCTS, EXTRAHEPATIC). Primary biliary cirrhosis involves the destruction of small intra-hepatic bile ducts and bile secretion. Secondary biliary cirrhosis is produced by prolonged obstruction of large intrahepatic or extrahepatic bile ducts from a variety of causes.Cholangitis, Sclerosing: Chronic inflammatory disease of the BILIARY TRACT. It is characterized by fibrosis and hardening of the intrahepatic and extrahepatic biliary ductal systems leading to bile duct strictures, CHOLESTASIS, and eventual BILIARY CIRRHOSIS.Copyright: It is a form of protection provided by law. In the United States this protection is granted to authors of original works of authorship, including literary, dramatic, musical, artistic, and certain other intellectual works. This protection is available to both published and unpublished works. (from Circular of the United States Copyright Office, 6/30/2008)Rare Diseases: A large group of diseases which are characterized by a low prevalence in the population. They frequently are associated with problems in diagnosis and treatment.Charities: Social welfare organizations with programs designed to assist individuals in need.United StatesAbscess: Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection.Down Syndrome: A chromosome disorder associated either with an extra chromosome 21 or an effective trisomy for chromosome 21. Clinical manifestations include hypotonia, short stature, brachycephaly, upslanting palpebral fissures, epicanthus, Brushfield spots on the iris, protruding tongue, small ears, short, broad hands, fifth finger clinodactyly, Simian crease, and moderate to severe INTELLECTUAL DISABILITY. Cardiac and gastrointestinal malformations, a marked increase in the incidence of LEUKEMIA, and the early onset of ALZHEIMER DISEASE are also associated with this condition. Pathologic features include the development of NEUROFIBRILLARY TANGLES in neurons and the deposition of AMYLOID BETA-PROTEIN, similar to the pathology of ALZHEIMER DISEASE. (Menkes, Textbook of Child Neurology, 5th ed, p213)Abnormalities, MultipleDental Prophylaxis: Treatment for the prevention of periodontal diseases or other dental diseases by the cleaning of the teeth in the dental office using the procedures of DENTAL SCALING and DENTAL POLISHING. The treatment may include plaque detection, removal of supra- and subgingival plaque and calculus, application of caries-preventing agents, checking of restorations and prostheses and correcting overhanging margins and proximal contours of restorations, and checking for signs of food impaction.Genetics, Medical: A subdiscipline of human genetics which entails the reliable prediction of certain human disorders as a function of the lineage and/or genetic makeup of an individual or of any two parents or potential parents.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.Heart Septal Defects, Ventricular: Developmental abnormalities in any portion of the VENTRICULAR SEPTUM resulting in abnormal communications between the two lower chambers of the heart. Classification of ventricular septal defects is based on location of the communication, such as perimembranous, inlet, outlet (infundibular), central muscular, marginal muscular, or apical muscular defect.Pulmonary Valve: A valve situated at the entrance to the pulmonary trunk from the right ventricle.Pulmonary Valve Stenosis: The pathologic narrowing of the orifice of the PULMONARY VALVE. This lesion restricts blood outflow from the RIGHT VENTRICLE to the PULMONARY ARTERY. When the trileaflet valve is fused into an imperforate membrane, the blockage is complete.Tetralogy of Fallot: A combination of congenital heart defects consisting of four key features including VENTRICULAR SEPTAL DEFECTS; PULMONARY STENOSIS; RIGHT VENTRICULAR HYPERTROPHY; and a dextro-positioned AORTA. In this condition, blood from both ventricles (oxygen-rich and oxygen-poor) is pumped into the body often causing CYANOSIS.Pulmonary Atresia: A congenital heart defect characterized by the narrowing or complete absence of the opening between the RIGHT VENTRICLE and the PULMONARY ARTERY. Lacking a normal PULMONARY VALVE, unoxygenated blood in the right ventricle can not be effectively pumped into the lung for oxygenation. Clinical features include rapid breathing, CYANOSIS, right ventricle atrophy, and abnormal heart sounds (HEART MURMURS).ArchivesTissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.Intellectual Disability: Subnormal intellectual functioning which originates during the developmental period. This has multiple potential etiologies, including genetic defects and perinatal insults. Intelligence quotient (IQ) scores are commonly used to determine whether an individual has an intellectual disability. IQ scores between 70 and 79 are in the borderline range. Scores below 67 are in the disabled range. (from Joynt, Clinical Neurology, 1992, Ch55, p28)Chromosome Mapping: Any method used for determining the location of and relative distances between genes on a chromosome.Chromosome Deletion: Actual loss of portion of a chromosome.Chromosome Banding: Staining of bands, or chromosome segments, allowing the precise identification of individual chromosomes or parts of chromosomes. Applications include the determination of chromosome rearrangements in malformation syndromes and cancer, the chemistry of chromosome segments, chromosome changes during evolution, and, in conjunction with cell hybridization studies, chromosome mapping.Karyotyping: Mapping of the KARYOTYPE of a cell.Keratins: A class of fibrous proteins or scleroproteins that represents the principal constituent of EPIDERMIS; HAIR; NAILS; horny tissues, and the organic matrix of tooth ENAMEL. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms a coiled-coil alpha helical structure consisting of TYPE I KERATIN and a TYPE II KERATIN, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. alpha-Keratins have been classified into at least 20 subtypes. In addition multiple isoforms of subtypes have been found which may be due to GENE DUPLICATION.Hepatocyte Nuclear Factor 6: A onecut transcription factor that regulates expression of GENES involved in EMBRYONIC DEVELOPMENT of the PANCREAS and LIVER.Rosaniline Dyes: Compounds that contain the triphenylmethane aniline structure found in rosaniline. Many of them have a characteristic magenta color and are used as COLORING AGENTS.Biliary Tract: The BILE DUCTS and the GALLBLADDER.Zebrafish Proteins: Proteins obtained from the ZEBRAFISH. Many of the proteins in this species have been the subject of studies involving basic embryological development (EMBRYOLOGY).Zebrafish: An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. They are used in embryological studies and to study the effects of certain chemicals on development.Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the RETINA and SCLERA.Choroid Diseases: Disorders of the choroid including hereditary choroidal diseases, neoplasms, and other abnormalities of the vascular layer of the uvea.Fluorescein Angiography: Visualization of a vascular system after intravenous injection of a fluorescein solution. The images may be photographed or televised. It is used especially in studying the retinal and uveal vasculature.Fundus Oculi: The concave interior of the eye, consisting of the retina, the choroid, the sclera, the optic disk, and blood vessels, seen by means of the ophthalmoscope. (Cline et al., Dictionary of Visual Science, 4th ed)Hypopigmentation: A condition caused by a deficiency or a loss of melanin pigmentation in the epidermis, also known as hypomelanosis. Hypopigmentation can be localized or generalized, and may result from genetic defects, trauma, inflammation, or infections.Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes.Eye Abnormalities: Congenital absence of or defects in structures of the eye; may also be hereditary.Heart Defects, Congenital: Developmental abnormalities involving structures of the heart. These defects are present at birth but may be discovered later in life.

Defects in mouse mammary gland development caused by conditional haploinsufficiency of Patched-1. (1/67)

In vertebrates, the hedgehog family of cell signaling proteins and associated downstream network components play an essential role in mediating tissue interactions during development and organogenesis. Loss-of-function or misexpression mutation of hedgehog network components can cause birth defects, skin cancer and other tumors. The mammary gland is a specialized skin derivative requiring epithelial-epithelial and epithelial-stromal tissue interactions similar to those required for development of other organs, where these interactions are often controlled by hedgehog signaling. We have investigated the role of the Patched-1 (Ptc1) hedgehog receptor gene in mammary development and neoplasia. Haploinsufficiency at the Ptc1 locus results in severe histological defects in ductal structure, and minor morphological changes in terminal end buds in heterozygous postpubescent virgin animals. Defects are mainly ductal hyperplasias and dysplasias characterized by multilayered ductal walls and dissociated cells impacting ductal lumens. This phenotype is 100% penetrant. Remarkably, defects are reverted during late pregnancy and lactation but return upon involution and gland remodeling. Whole mammary gland transplants into athymic mice demonstrates that the observed dysplasias reflect an intrisic developmental defect within the gland. However, Ptc1-induced epithelial dysplasias are not stable upon transplantation into a wild-type epithelium-free fat pad, suggesting stromal (or epithelial and stromal) function of Ptc1. Mammary expression of Ptc1 mRNA is both epithelial and stromal and is developmentally regulated. Phenotypic reversion correlates with developmentally regulated and enhanced expression of Indian hedgehog (Ihh) during pregnancy and lactation. Data demonstrate a critical mammary role for at least one component of the hedgehog signaling network and suggest that Ihh is the primary hedgehog gene active in the gland.  (+info)

The expression of Jagged1 in the developing mammalian heart correlates with cardiovascular disease in Alagille syndrome. (2/67)

The establishment of the cardiovascular system represents an early, critical event essential for normal embryonic development, and defects in cardiovascular development are a frequent cause of both in utero and neonatal demise. Congenital cardio-vascular malformations, the most frequent birth defect, can occur as isolated events, but are frequently presented clinically within the context of a constellation of defects that involve multiple organs and that define a specific syndrome. In addition, defects can be a primary effect of gene mutations or result from secondary effects of altered cardiac physiology. Alagille syndrome (AGS) is an autosomal dominant disorder characterized by developmental abnormalities of the heart, liver, eye, skeleton and kidney. Congenital heart defects, the majority of which affect the right-sided or pulmonary circulation, contribute significantly to mortality in AGS patients. Recently, mutations in Jagged1 ( JAG1 ), a conserved gene of the Notch intercellular signaling pathway, have been found to cause AGS. In order to begin to delineate the role of JAG1 in normal heart development we have studied the expression pattern of JAG1 in both the murine and human embryonic heart and vascular system. Here, we demonstrate that JAG1 is expressed in the developing heart and multiple associated vascular structures in a pattern that correlates with the congenital cardiovascular defects observed in AGS. These data are consistent with an important role for JAG1 and Notch signaling in early mammalian cardiac development.  (+info)

Living related donor liver transplantation in a patient with severe aortic stenosis. (3/67)

We report the successful anaesthetic management of a young girl with Alagille's syndrome and severe aortic stenosis (resting pressure gradient 88 mm Hg) undergoing living related donor liver transplantation (LRDLT). The patient had end-stage liver disease and LRDLT was performed before replacement of the aortic valve. Anaesthesia was conducted uneventfully with the aid of a pulmonary artery catheter. Intra-aortic balloon pumping was used in the perioperative period for protection against myocardial ischaemia. Total clamping of the inferior vena cava was avoided during surgery and volume administration was guided by the pulmonary artery pressure. A stable circulation was maintained in the reperfusion period. The patient was discharged from hospital on day 54 after operation with normal liver function. Two years later her aortic valve was replaced successfully.  (+info)

JAGGED1 expression in human embryos: correlation with the Alagille syndrome phenotype. (4/67)

Alagille syndrome (AGS, MIM 118450) is an autosomal dominant disorder with a variable phenotype characterised by hepatic, eye, cardiac, and skeletal malformations and a characteristic facial appearance. Mutations within the gene JAGGED1 (JAG1), which encodes a ligand for NOTCH receptor(s), has been shown to cause Alagille syndrome. Interactions of NOTCH receptors and their ligands influence cell fate decisions in several developmental pathways. We report the tissue expression of JAG1 in human embryos. We have performed tissue in situ hybridisation on human embryos aged 32-52 days using (35)S labelled riboprobes for JAG1. JAG1 is expressed in the distal cardiac outflow tract and pulmonary artery, major arteries, portal vein, optic vesicle, otocyst, branchial arches, metanephros, pancreas, mesocardium, around the major bronchial branches, and in the neural tube. We conclude that JAG1 is expressed in the structures affected in Alagille syndrome, such as the pulmonary artery, anterior chamber of the eye, and face.  (+info)

Does liver transplantation affect growth pattern in Alagille syndrome? (5/67)

Alagille syndrome (AGS) is frequently associated with growth failure, which has been attributed to concurrent congenital anomalies, cholestasis, and malabsorption and/or malnutrition. However, the underlying cause of the growth failure is not well understood. Our objective is to analyze the growth pattern in 26 patients with AGS and the possible effect that orthotopic liver transplantation (OLT) may have on this pattern. The standardized height, weight, and growth velocity of 26 pair-matched patients with AGS were compared. Thirteen patients underwent OLT. Repeated-measure ANOVA methods were used for the statistical analysis. The overall mean standardized height (z score) was -2.92 in the OLT group versus -1.88 in the non-OLT group (P =.03). The overall mean standardized weight was -1. 21 in the non-OLT group and -1.67 in the OLT group (P =.23). In 15 patients, birth weight was 2.82 +/- 0.4 kg, for a mean standardized weight of -0.95, and weight at diagnosis was 4.53 +/- 2.12 kg, for a mean standardized weight of -1.56. Bone age was delayed in the 9 patients who underwent bone-age analysis. Growth hormone therapy administered to 2 patients did not improve growth. Patients with AGS had growth failure secondary to other factors in addition to liver disease. Growth failure beginning in the prenatal period supports a genetic basis for this feature. Growth improvement up to normal levels should not be expected as a benefit of OLT in these patients. Growth failure as a primary indication for OLT should be cautiously examined in patients with AGS.  (+info)

Defective intracellular transport and processing of JAG1 missense mutations in Alagille syndrome. (6/67)

Jagged1 (JAG1) is a cell surface ligand in the Notch signaling pathway and mutations in this gene cause Alagille syndrome (AGS). JAG1 mutations have been identified in 60-70% of AGS patients studied, and these include total gene deletions ( approximately 6%), protein-truncating mutations (insertions, deletions and nonsense mutations) (82%) and missense mutations (12%). Based on the finding that total JAG1 deletions cause AGS, haploinsufficiency has been hypothesized to be a mechanism for disease causation; however, the mechanism by which missense mutations cause disease is not understood. To date, 25 unique missense mutations have been observed in AGS patients. Missense mutations are non-randomly distributed across the protein with clusters at the 5' end of the protein, in the conserved DSL domain, and two clusters within the EGF repeats. To understand the effect of the missense mutations on protein localization and function, we have studied four missense mutations (R184H, L37S, P163L and P871R). In two assays of JAG1 function, R184H and L37S are associated with loss of Notch signaling activity relative to wild-type JAG1. Neither R184H or L37S is present on the cell surface and both are abnormally glycosylated. Furthermore, these mutations lead to abnormal accumulation of the protein, possibly in the endoplasmic reticulum. Both P163L and P871R are associated with normal levels of Notch signaling activity and are present on the cell surface, consistent with these changes being polymorphisms rather than disease-causing mutations.  (+info)

Parental mosaicism of JAG1 mutations in families with Alagille syndrome. (7/67)

The Alagille syndrome (AGS), a congenital disorder affecting liver, heart, skeleton and eye in association with a typical face, is an autosomal dominant disease with nearly complete penetrance and variable expression. AGS is caused by mutations in the developmentally important JAG1 gene. In our mutation screening, where 61 mutations in JAG1 were detected, we identified five cases where mosaicism is present. Our results point to a significant frequency of mosaicism for JAG1 mutations in AGS of more than 8.2%. Because mosaicism may be associated with a very mild phenotype, the appropriate diagnosis of AGS and consequently the determination of the recurrence risk can be complicated.  (+info)

Outcome of liver disease in children with Alagille syndrome: a study of 163 patients. (8/67)

BACKGROUND AND AIMS: Various opinions have been expressed as to the long term prognosis of liver disease associated with Alagille syndrome (AGS). PATIENTS AND METHODS: We reviewed the outcome of 163 children with AGS and liver involvement, investigated from 1960 to 2000, the end point of the study (median age 10 years (range 2 months to 44 years)) being death, liver transplantation, or the last visit. RESULTS: At the study end point, of the 132 patients who presented with neonatal cholestatic jaundice, 102 remained jaundiced, 112 had poorly controlled pruritus, and 40 had xanthomas; cirrhosis was found in 35/76 livers, varices in 25/71 patients, and liver transplantation had been carried out in 44 patients (33%). Forty eight patients died, 17 related to complications of liver disease. Of 31 patients who did not present with neonatal cholestatic jaundice, five were jaundiced at the study end point, 17 had well controlled pruritus, and none had xanthomas; cirrhosis was found in 6/18 patients, varices in 4/11, and none underwent liver transplantation. Nine patients died, two of liver disease. In the whole series, actuarial survival rates with native liver were 51% and 38% at 10 and 20 years, respectively, and overall survival rates were 68% and 62%, respectively. Neonatal cholestatic jaundice was associated with poorer survival with native liver (p=0.0004). CONCLUSIONS: The prognosis of liver disease in AGS is worse in children who present with neonatal cholestatic jaundice. However, severe liver complications are possible even after late onset of liver disease, demanding follow up throughout life.  (+info)

Alagille syndrome is an autosomal dominant disorder with high penetrance but variable expressivity. Alagille syndrome 1 (ALGS1; MIM 118450) is caused by mutations in the JAG1 gene, encoding jagged-1, a ligand for the Notch receptors. Alagille syndrome 2 (ALGS2; MIM 610205) is caused by mutations in NOTCH2, which encodes a transmembrane Notch receptor. Interactions between Notch ligands and receptors regulate signaling pathways important for cell fate determination. The main clinical findings of Alagille syndrome include cholestasis due to bile duct paucity, congenital heart defects, skeletal abnormalities, a characteristic facial appearance, eye abnormalities, and renal disease. Cardiovascular findings include tetralogy of Fallot, peripheral pulmonary artery stenosis, atrial and/or ventricular septal defects, and coarctation of the aorta. Butterfly vertebra is the most common skeletal finding, particularly in individuals with JAG1 mutations. Other findings include narrowing of interpeduncular ...
Alagille syndrome is an autosomal dominant disorder with high penetrance but variable expressivity. Alagille syndrome 1 (ALGS1; MIM 118450) is caused by mutations in the JAG1 gene, encoding jagged-1, a ligand for the Notch receptors. Alagille syndrome 2 (ALGS2; MIM 610205) is caused by mutations in NOTCH2, which encodes a transmembrane Notch receptor. Interactions between Notch ligands and receptors regulate signaling pathways important for cell fate determination. The main clinical findings of Alagille syndrome include cholestasis due to bile duct paucity, congenital heart defects, skeletal abnormalities, a characteristic facial appearance, eye abnormalities, and renal disease. Cardiovascular findings include tetralogy of Fallot, peripheral pulmonary artery stenosis, atrial and/or ventricular septal defects, and coarctation of the aorta. Butterfly vertebra is the most common skeletal finding, particularly in individuals with JAG1 mutations. Other findings include narrowing of interpeduncular ...
1. Alagille syndrome: spectrum of clinical presentation in India. http://www.ncbi.nlm.nih.gov/pubmed/22692667. Gupta P, Bhakhri BK, Paul P.. Indian J Gastroenterol.2012Jun;31(3):149-50.doi:10.1007/s12664-012-0199-8. No abstract available.. PMID: 22692667 [PubMed - indexed for MEDLINE]. 2. Alagille syndrome: a rare disease in an adolescent.. http://www.ncbi.nlm.nih.gov/pubmed/22678460. Guru Murthy GS, Rana BS, Das A, Thapa BR, Duseja AK, Dhiman RK, Chawla YK.. Dig Dis Sci. 2012Nov;57(11):3035-7. doi:10.1007/s10620-012-2226-0.Epub 2012Jun 8. No abstract. available.. PMID: 22678460 [PubMed - indexed for MEDLINE]. 3. Alagille syndrome with prominent skin manifestations.. http://www.ncbi.nlm.nih.gov/pubmed/16394388. Sengupta S, Das JK, Gangopadhyay A.. Indian J Dermatol Venereol Leprol. 2005 Mar-Apr;71(2):119-21.. PMID: 16394388 [PubMed - indexed for MEDLINE] Free Article. 4. Alagille syndrome.. http://www.ncbi.nlm.nih.gov/pubmed/12420920. Shendge H, Tullu MS, Shenoy A, Chaturvedi R, Kamat JR, Khare ...
TY - JOUR. T1 - Surgical reconstruction of peripheral pulmonary artery stenosis in Williams and Alagille syndromes. AU - Monge, Michael C.. AU - Mainwaring, Richard D.. AU - Sheikh, Ahmad Y.. AU - Punn, Rajesh. AU - Reddy, V. Mohan. AU - Hanley, Frank L.. PY - 2013/2/1. Y1 - 2013/2/1. N2 - Objectives: Peripheral pulmonary artery stenosis is a rare congenital heart defect frequently found in association with Williams and Alagille syndromes. Controversy exists regarding the optimal treatment of peripheral pulmonary artery stenosis, with most centers favoring catheter-based interventions. In contrast, we have preferentially used surgical reconstruction of peripheral pulmonary artery stenosis. The purpose of the present study was to review our experience with surgical reconstruction of peripheral pulmonary artery stenosis. Methods: We performed a retrospective review of patients who underwent surgical reconstruction of peripheral pulmonary artery stenosis. A total of 16 patients were identified: 7 ...
Since the first descriptions of Alagille syndrome (syndromic bile duct paucity) 30 years ago, our appreciation of the clinical variability and complexity of this disorder has grown. In addition to the liver, Alagille syndrome is associated with abnormalities that involve the heart, eye, skeleton, ki …
Alagille syndrome is a genetic disorder affecting heart, liver and other body systems. Alagille syndrome pictures, symptoms, causes and treatment explained.
The patient was a 15-year-old girl with an established diagnosis of Alagille syndrome (AS) since early life. Her medical history was significant for systemic manifestations of AS including liver transplantation and pulmonary artery balloon dilation. She had an unusual triangular facies characterized by a broad overhanging forehead, deep set, hyperteloric eyes and small pointed chin. Her bestcorrected visual acuity was 1.0 in both eyes. Slit-lamp examination was positive for posterior embryotoxon in both eyes. Funduscopy revealed diffuse choroidal hypopigmentation with increased visibility of the choroidal vessels and symmetric, well-circumscribed macular discoloration (Figure 1). A circumferential chorioretinal atrophy was also detected in the peripheral retina (Figure 1). Fundus autofluorescence (FAF) imaging clearly defined hypofluorescent areas in the peripapillary regions that extended along the macula and had a sleep mask appearance (Figure 2). Peripheral circumferential chorioretinal ...
Alagille syndrome (ALGS) is an autosomal dominant condition, primarily caused by mutations in JAGGED1. ALGS is defined by cholestatic liver disease, cardiac disease and involvement of the face, skeleton, and eyes with variable expression of these features. Renal involvement has been reported though not formally described. The objective of this study was to systematically characterize the renal involvement in ALGS. We performed a retrospective review of 466 JAGGED1 mutation-positive ALGS patients. Charts were reviewed for serum biochemistries, renal ultrasounds or other imaging, urinalysis, and clinical reports from pediatric nephrologists. The clinical data were reviewed by two pediatric hepatologists and a pediatric nephrologist. Of 466 charts reviewed we found 187 yielded evaluable renal information. Of these, 73/187 were shown to have renal involvement, representing 39% of the study cohort. Renal dysplasia was the most common anomaly seen. Genotype analysis of the JAGGED1 mutations in the ...
Alagille syndrome (ALGS), also known as arteriohepatic dysplasia, is a rare autosomal dominant genetic disorder caused by mutations in the Notch signalling pathway
My son is 15 weeks old and has recently been diagnosed with Alagille syndrome. Over the last couple of weeks he has started itching his eyes and face. Im not sure he can co-ordinate his hand to the...
Alagille syndrome is an autosomal dominant inherited disorder associated with liver, heart, eye and skeletal abnormalities, and characteristic facial features.
Alagille syndrome is an inherited condition in which bile builds up in the liver because there are too few bile ducts to drain the bile. This results in liver damage.
Describes Alagille syndrome, a rare, inherited disorder that affects the liver. Covers the causes, symptoms, diagnosis, treatment, and long-term outlook.
Hypoplasia of the hepatic ducts, congenital pulmonary artery stenosis, facial abnormalities, and other congenital malformations, particularly skeletal.
Methods Pulmonary stenosis and a large ventricular septal defect (VSD) had been diagnosed prenatally. Postnatal echocardiogram revealed an APV, pulmonary stenosis, a large sub-aortal VSD, and right ventricular hypertrophy.. Genetic analysis of the JAG-1 gene showed a frame-shift-mutation in exon 12 of the JAG-1 gene that had not been described before.. The patient underwent corrective heart surgery at 9 months of age. The VSD and the native pulmonary artery orifice were closed surgically. A valved xenograft conduit (Contegra®, 14 mm) was implanted between the RV and the pulmonary artery.. ...
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The Alagille diagnosis clicked a puzzle piece in place. We may never have known if she had biliary atresia--her liver is too damaged to tell with a biopsy or during transplant at this point. But with a positive genetic test result, that mystery has been solved. We know definitively what has caused the liver failure. And we also know why were sitting around in July without the same rate of rapid decline that was happening October - February. Alagille Syndrome patients have no anticipated rhythm or pattern to their liver failure. While biliary atresia patients tend to decline steadily and/or rapidly at different times, ALGS patients can plateau, decline steadily, plateau, decline rapidly, etc all at varying times and speeds. This plateau that Brooklyn seemed to have hit this past spring was just that. And it explains why she had seemed to be declining so rapidly in the fall--because she was. She is still in liver failure and still needs a transplant, but her decline has transitioned into a period ...
A white line on the peripheral edge of the inner surface of the cornea that can be seen during an examination with a slit lamp. Posterior embryotoxon does not affect vision but is a sign of a malformed drainage system of the eye. This phenomenon was once called Axenfeld anomaly but is now recognized as occurring in almost all forms of Axenfeld-Rieger spectrum. Posterior embryotoxon can occur in patients with no other eye abnormalities, people who do not have glaucoma, or individuals who have certain syndromes that are not normally eye-related, such as Alagille syndrome with liver disease. Strands of iris are sometimes attached to the posterior embryotoxon ...
A white line on the peripheral edge of the inner surface of the cornea that can be seen during an examination with a slit lamp. Posterior embryotoxon does not affect vision but is a sign of a malformed drainage system of the eye. This phenomenon was once called Axenfeld anomaly but is now recognized as occurring in almost all forms of Axenfeld-Rieger spectrum. Posterior embryotoxon can occur in patients with no other eye abnormalities, people who do not have glaucoma, or individuals who have certain syndromes that are not normally eye-related, such as Alagille syndrome with liver disease. Strands of iris are sometimes attached to the posterior embryotoxon ...
JAG1, the gene for the Jagged-1 ligand (Jag1) in the Notch signaling pathway, is variably mutated in Alagille Syndrome (ALGS). ALGS patients have skeletal defects, and additionally JAG1 has been shown to be associated with low bone mass through genome wide association studies. Plating human osteoblast precursors (mesenchymal stem cells -- hMSC) on Jag1 is sufficient to induce osteoblast differentiation; however, exposure of mouse MSC (mMSC) to Jag1 actually inhibits osteoblastogenesis. Overexpression of the notch-2 intracellular domain (NICD) is sufficient to mimic the effect of Jag1 on hMSC osteoblastogenesis, while blocking Notch signaling with a gamma-secretase inhibitor or with dominant negative mastermind inhibits Jag1 induced hMSC osteoblastogenesis. In pursuit of interacting signaling pathways, we discovered that treatment with a PKCδ inhibitor abrogates Jag1 induced hMSC osteoblastogenesis. Jag1 results in rapid PKCδ nuclear translocation and kinase activation. Furthermore, Jag1 stimulates the
The JAG1 gene is associated with autosomal dominant Alagille syndrome (MedGen UID: 365434) and tetralogy of Fallot (MedGen UID: 21498).
Anatomy and Development of the Liver -- Normal functional biology of the liver -- Laboratory assessment of hepatic injury and function -- Mechanisms of Liver Injury -- Radiology of the liver in children -- Phenotypes of liver disease in infants, children and adolescents children -- Psychosocial, cognitive, and quality of life considerations in the child with liver disease and their family children -- Metabolic liver disease -- Part 1 -- Metabolic liver disease -- Part 2 -- Neonatal Hemochromatosis and Gestational Alloimmune Liver Disease -- Alagille Syndrome -- Idiopathic Neonatal Hepatitis and its Differential Diagnoses -- Biliary atresia -- Choledochal Cysts and fibrocystic diseases of the liver -- Infections of the Liver -- Autoimmune Hepatitis and Sclerosing Cholangitis -- Parental Nutrition Associated Liver Disease in Pediatric Patients: Strategies for Treatment and Prevention -- Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis -- Drug induced liver injury in children: A ...
Cholestatic liver diseases in childhood frequently result in growth retardation. The pathophysiology is usually multifactoral including reduced calorie intake, abnormal protein metabolism, fat and fat soluble vitamin malabsorption, increased energy expenditure, pancreatic insufficiency, accompanying infections and genetic disposition. All children with cholestatic liver diseases should undergo an assessment for their nutritional status and dietary intake and receive dietary counseling from a dietitian with monitoring of intake to ensure adequate energy and nutrient intake. After liver transplantation growth improves in the majority of children with good liver function. However some children, especially with genetic diseases such as Alagille syndrome, PFIC or CF do not grow normally. In selected cases therapy with growth hormone should be considered ...
High-resolution chromosome analysis of a 19-year-old female proband with syndromic intrahepatic ductular hypoplasia (Alagille syndrome, AWS) revealed an interstitial deletion of chromosome 20p with breakpoints provisionally located in or close to p11.22 and p12.2. Southern blots from digests of DNA of the proband and her chromosomally normal parents were hybridized with the human DNA probes pR12.21, HuPrPcDNA2, and pDS6-SgI, which have been mapped to the region 20 (p12-pter), and rehybridized with the F IX probe for calibration. Comparing the hybridization signals of the normally sized DNA fragments of the family, we found no evidence for loss of any of the three tested distal chromosome 20p loci in our proband. Furthermore, in situ hybridization with HuPrPcDNA2 revealed a specific accumulation of grains at or around the faint distal G band suspected to represent all or most of band p12.3 of the probands deleted 20p and at p12 of the normal chromosome 20. Thus the AWS of our proband is ...
Our laboratory studies genes important for embryonic development in mice, and the relation between mutations in these genes and both congenital and acquired human disease. Our analyses focus on the Notch pathway, an evolutionarily conserved cell communication and signaling system, and on genes of the Snail superfamily, which encode transcriptional repressor proteins.. We have created and analyzed numerous genetically engineered mouse models to understand the essential functions of individual components of these pathways. We have also generated mouse models for inherited human disease syndromes such as Alagille syndrome, and for common birth defects such as cleft palate, craniosynostosis, and congenital heart defects, such as outflow tract patterning defects and patent ductus arteriosus. Current areas of interest include the role of Notch ligands in cardiovascular development, and in skeletal muscle and mesenchymal stem cells.. ...
The treatment of alagille syndrome is directed toward the specific symptoms that are apparent in each individual. Pediatricians, gastroenterologists, cardiologists, ophthalmologists, and other healthcare professionals may need to systematically and comprehensively plan treatment. Supplemental vitamins and nutrients may be needed. In some cases, a nasogastric tube or a gastrostomy tube must be used in order to ensure sufficient calorie absorption. The drug ursodeoxycholic acid is given to help improve bile flow, which can lead to a reduction in some symptoms such as itching (pruritus) or fatty deposits (xanthomas). Not all patients respond positively to pharmacologic and dietary therapies and may need to be treated via a surgical procedure known as partial biliary diversion. This surgical procedure is used to disrupt or divert recirculation of bile acids between the liver and the gastrointestinal tract. Liver transplantation may be necessary for patients with refractory disease. Cardiac or ...
Genetics (from Ancient Greek γενετικός genetikos, "genite" and that from γένεσις genesis, "origin"), a discipline of biology, is the science of heredity and variation in living organisms. Articles (arranged alphabetically) related to genetics include: Contents: Top 0-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z 3 end 5 end Acentric chromosome Achondroplasia Active site Adams Curse Adaptation Adenine Adenosine Adenovirus Adenosine diphosphate (ADP) Ala Alagille syndrome Albino Alcoholism Alkylating agent Allele Allele frequency Alleles Allopolyploid Allosteric protein Allozyme Alternative splicing Altruism Alu family Alzheimers disease Amber codon Ames test Amino acid Amino acid sequence Amino acids Amniocentesis Amorph AMP Amphidiploid Amplification Anagenesis Anaphase Aneuploid Aneuploid cell Aneuploidy Angelman syndrome Angiosperm Animal model Annealing Annotation Antibody Anticipation Anticoding strand Anticodon Antigen Antimorph Antiparallel Antisense Antisense ...
Researchers from the University of Pennsylvania School of Veterinary Medicine have discovered that a protein called Jagged-1 stimulates human stem cells to differentiate into bone-producing cells. This protein could help both human and animal patients heal from bone fractures faster and may form the basis of treatments for a rare metabolic condition called Alagille syndrome.. The study, published in the journal Stem Cells, was authored by three members of Penn Vet´s departments of Clinical Studies-New Bolton Center and Animal Biology: postdoctoral researchers Fengchang Zhu and Mariya T. Sweetwyne and associate professor Kurt Hankenson, who also holds the Dean W. Richardson Chair in Equine Disease Research.. Last November, on the promise of these and other findings, Hankenson and his former doctoral student Mike Dishowitz launched a company, Skelegen, through Penn´s Center for Technology Transfer UPstart program. Skelegen´s focus is to continue to develop and improve a system for delivering ...
J:58809 Loomes KM, Underkoffler LA, Morabito J, Gottlieb S, Piccoli DA, Spinner NB, Baldwin HS, Oakey RJ, The expression of Jagged1 in the developing mammalian heart correlates with cardiovascular disease in Alagille syndrome. Hum Mol Genet. 1999 Dec;8(13):2443-9 ...
This post provides links to various resources on getting started with Bayesian modelling using JAGS and R. It discusses: (1) what is JAGS; (2) why you might want to perform Bayesian modelling using JAGS; (3) how to install JAGS; (4) where to find further information on JAGS; (5) where to find examples of JAGS scripts in action; (6) where to ask questions; and (7) some interesting psychological applications of Bayesian modelling.. ...
Många fina växter på A du samlat här. Tittade i din helgsummering också och ler... ..igenkännande. Första trädgården var inte min egen utan jag projekterade i mammas. Var tom så uttråkad när jag var au-pair i England som 18-åring att jag frågade om jag kunde få gräva om och rensa upp några rabatter. Frun i huset blev väldigt positivt överraskad när hon kom hem och for iväg och köpte nya växter. Så har det fortsatt - över i samlande. 17 nya Hostor beställda till våren men kanske att nån mer åker med innan jag blir klar ...
Marit ... vilka fantastiska pioner. Den djupt vinröda, underbar! Och jag som älskar blommor i mild gul nyans blev helt salig när jag såg din Cheddar Gold. Och Sorbet, det är ju så att man blir sugen på att äta en kall, god sorbet :) Vi har också fått massor av regn, rena slagregnen som verkligen slår ner allt. Igår var jag ute och plockade in en bukett av pioner och det var jag glad åt för när jag hade gjort det kom ett riktigt slagregn, igen. Det är en märklig sommar i år men ... det är ändå sommar och mellan regnen så får vi njuta ...
Ja, så länge som jag har en sittplats så klarar jag av att läsa på bussen. Men det är riktigt svårt att hålla kvar koncentrationen på stadsbussarna... ^^ ...
Välkommen till veterinär Elisabeth Hemberg, jag har stor erfarenhet av dräktighetsproblem hos ston. Ston mottages för inseminering med färsk eller frusen sperma.
In this video you will receive teachings and blessings to transform liver conditions including its manifestation in these forms: fatty liver, liver disease, liver cancer, alcoholism, Alagille Syndrome, Alpha 1 Anti-Trypsin Deficiency, Autoimmune Hepatitis, Biliary Atresia, Cirrhosis and Complications, Cystic Disease of the Liver,Fatty Liver Disease, Galactosemia, Gallstones, Gilberts Syndrome, Hemochromatosis, Liver Cancer, Liver disease in pregnancy, Lysosomal Acid Lipase Deficiency (LALD),Neonatal Hepatitis, Primary Biliary Cholangitis, Primary Biliary Cirrhosis, Primary Sclerosing Cholangitis, Porphyria, Reyes Syndrome, Sarcoidosis, Toxic Hepatitis, Type 1 Glycogen Storage Disease, Tyrosinemia, Viral Hepatitis A, B, C, Hepatitis B,Hepatitis A, Hepatitis C, Wilson Disease, Liver Transplants, Operations, Surgery, and other related conditions. You may receive insight or answers to the following types of questions: "Why am I so angry? How can I heal my anger? How can I heal my liver? With a lot ...
Neurogenic locus notch homolog protein 2 also known as notch 2 is a protein that in humans is encoded by the NOTCH2 gene. NOTCH2 is associated with Alagille syndrome and Hajdu-Cheney syndrome. Notch 2 is a member of the notch family. Members of this Type 1 transmembrane protein family share structural characteristics including an extracellular domain consisting of multiple epidermal growth factor-like (EGF) repeats, and an intracellular domain consisting of multiple, different domain types. Notch family members play a role in a variety of developmental processes by controlling cell fate decisions. The Notch signaling network is an evolutionarily conserved intercellular signaling pathway that regulates interactions between physically adjacent cells. In Drosophilia, notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signaling pathway that plays a key role in development. Homologues of the notch-ligands have also been identified in human, but precise ...
is a biopharmaceutical company specializing in identifying, developing and delivering life-changing therapies to people living with rare disease. The Companys approach centers on its pipeline featuring sparsentan, a product candidate in late-stage development for focal segmental glomerulosclerosis (FSGS) and IgA nephropathy (IgAN), rare disorders characterized by progressive scarring of the kidney often leading to end-stage renal disease. Research in additional rare diseases is also underway, including partnerships with leaders in patient advocacy and government research to identify potential therapeutics for NGLY1 deficiency and Alagille syndrome, conditions with no approved treatment options. Retrophins R&D efforts are supported by revenues from the Companys commercial products Chenodal®, Cholbam®, Thiola® and Thiola EC™.. Retrophin.com. Forward Looking Statements. This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation ...
TY - JOUR. T1 - Case report. T2 - Paucity of interlobular bile ducts in Chinese children. AU - Chiu, Hsiu Hui. AU - Chang, Mei Hwei. AU - Chen, Chi Long. AU - Hsu, Hong Yuan. AU - Ni, Yen Hsuan. PY - 1996. Y1 - 1996. N2 - Sixteen Chinese children with cholestasis since early infancy were diagnosed to have paucity of interlobular bile ducts (PILED) or its equivalent. Twelve children belonged to the syndromic group of PILBD and four children belonged to the non-syndromic group. A definite histological diagnosis of bile duct paucity was established in only two children (aged 4 and 9 months) during the first percutaneous needle biopsy. In the remaining 14 children a varying degree of bile duct destruction was evident in the follow up percutaneous or wedge liver biopsies. The evolving changes were characterized by inflammatory infiltration near or at the ductal wall, the presence of dysmorphic ductules, the degeneration of ductal epithelia and a progressive decrease of interlobular bile ducts. Of 10 ...
Given variability in data and limitation to single institution cohorts in previous studies, the goal of this project was to better define which histologic features are the strongest predictors of biliary atresia (BA) and identify parameters that may be of prognostic significance. This study utilized data and slide review from cholestatic infants that were prospectively enrolled in the multicenter ChiLDReN network to determine which histologic features: (1) could distinguish BA from non-BA causes of cholestasis [N=227]; (2) varied with respect to clinical parameters (including age); and (3) correlated with clinical outcome in BA patients after hepatoportoenterostomy (HPE) [N=316]. Except for patient age, central review pathologists were blinded to all clinical information and scored 26 histologic features based on consensus. Bile plugs in portal tracts and portal tract edema, when seen without bile duct paucity or features of idiopathic neonatal hepatitis (giant cell transformation and ...
Childrens Liver Disease Foundation - UKs leading charity fighting childhood liver diseases inc Alagille, alpha 1, autoimmune, biliary atresia, PFIC
Childrens Liver Disease Foundation - UKs leading charity fighting childhood liver diseases inc Alagille, alpha 1, autoimmune, biliary atresia, PFIC
I december förra året ställde jag upp i Bokhoras julkalender-tävling och vann en bok. Det blev lite klydd men idag fick jag äntligen min fina bok. Wiiie! ...
My ds 14 months has had diarrhoea for 3 weeks now, apparently caused by his jags and teething. He leaks every night in bed and then all day so we hav
The light collection efficiency of an optical system is largely determined by a quantity known as numerical aperture. The numerical aperture of an optic is described as where n is the index of refraction of the media between the sample and the optic (nair 1.0, nwater 1.3, noil 1.51) and a is the angular aperture of the system, measured as the half-angle included by a cone with its apex at the sample and its base at the perimeter of the first surface of the collection optic when the sample is in.... ...
TY - JOUR. T1 - Living-related liver transplantation in children. T2 - The Parisian strategy to safely increase organ availability. AU - Révillon, Y.. AU - Michel, J. L.. AU - Lacaille, F.. AU - Sauvat, F.. AU - Farges, O.. AU - Belghiti, J.. AU - Rengeval, A.. AU - Jouvet, P.. AU - Sayegh, N.. AU - Sarnacki, S.. AU - Jan, D.. PY - 1999/5. Y1 - 1999/5. N2 - Purpose: The aim of the authors was to report their experience with living related liver transplantation (LRLT) in children, particularly focusing on the safety of the two-center Parisian strategy. Methods: The records of donors and recipients of 26 pediatric living-related donor liver transplantations performed between November 1994 and March 1998 were reviewed retrospectively. Donors were assessed 1 year after transplantation for medical and overall status. Results: Indications for LRLT included biliary atresia (n = 18), Bylers disease (n = 5), alpha-1-antitrypsin deficiency (n = 1), Alagille syndrome (n = 1), and undefined cirrhosis ...
american society of gene therapy, gene therapy, gene research, genes, chromosomes, units of heredity, cancer gene therapy, gene therapy systems, gene delivery, gene therapy research, biotechnology, human gene therapy, germ-line, cellular and gene therapy, european society of gene therapy, gene therapy research, aarskog syndrome, aase syndrome, ablepharon-macrostomia syndrome, acoustic neuroma, adie syndrome, adrenal hyperplasia, adrenoleukodystrophy, aicardi syndrome, alagille syndrome, albinism, alkaptonuria, alopecia areata, alpha-1 antitrypsin deficiency, alstrom syndrome, angelman syndrome, apert syndrome, arthrogryposis, ataxia, autism, bardet-biedl syndrome, barth syndrome, batten, beckwith-wiedemann syndrome, canavan, celiac, cerebrocostomandibular syndrome, charcot-marie-tooth disease, cleidocranial dysplasia, cockayne syndrome, coffin lowry syndrome, congenital cardiovascular disorders, congenital heart disease, congenital musculoskeletal disorders, congenital neurological disorders, congenital
The Notch protein is a transmembrane signaling protein responsible for regulating several important pathways among all metazoans including cell proliferation, differentiation, and death. Notch exists as one protein in Drosophila, but has four homologs in mice and humans (Notch1- 4). A defining component of the Notch protein is the presence of 29-36 tandem epidermal growth factor-like (EGF) repeats, small protein motifs defined by the presence of six cysteines forming three disulfide bonds. Defects in Notch have been linked to various diseases like Alagille syndrome and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). CADASIL is responsible for early onset of dementia in patients aged 40-50, along with migraines and stroke. CADASIL is characterized by the presence and accumulation of granular osmiophilic material (GOMs) and Notch3 extracellular domain in close proximity to vascular smooth muscle cells, eventually leading to the degradation of ...
Gastroenterology Alagille Syndrome Cholestasis Colic Colitis Congenital Hepatic Fibrosis Cyclic Vomiting Syndrome Diarrhea Encopresis Intestinal Enterokinase Deficiency Intestinal Malrotation Intestinal Polyposis Syndromes Intussusception Mallory-Weiss Syndrome Microvillus Inclusion Disease Neonatal Hemochromatosis Pediatric Appendicitis Pediatric Appendicitis Empiric Therapy Pediatric Appendicitis Organism-Specific Therapy Pediatric Biliary Atresia Pediatric Caroli Disease Pediatric Celiac Disease Pediatric Cholecystitis Pediatric Constipation Pediatric Crohn…
UniProtKB/Swiss-Prot : 74 Deafness, congenital heart defects, and posterior embryotoxon: An autosomal dominant disease characterized by mild to severe combined hearing loss, congenital heart defects, and posterior embryotoxon, a corneal abnormality consisting of a central collagen core surrounded by a thin layer of Descemets membrane and separated from the anterior chamber by a layer of endothelium. Congenital heart defects include tetralogy of Fallot, ventricular septal defect, or isolated peripheral pulmonic stenosis ...
This press release includes "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements, other than statements of historical fact, regarding, among other things: the plans for, or progress, scope, cost, duration or results or timing for availability of results of, development of A4250, including regarding the Phase 3 clinical program for A4250 in patients with PFIC; the target indication(s) for development, the size, design, population, location, conduct, objective, duration or endpoints of any clinical trial, or the timing for initiation or completion of or reporting of results from any clinical trial, including the double-blind Phase 3 PFIC trial for A4250; the size of the PFIC population, the Alagille population, the biliary atresia population or any other disease population for indications that may be targeted by Albireo; the potential benefits or competitive position of A4250; the potential benefits ...
"Alagille Syndrome". GeneReviews. PMID 20301450. Tidyman, W. E.; Rauen, K. A. (2009). "The RASopathies: developmental syndromes ... including Noonan syndrome, LEOPARD syndrome, Costello syndrome and cardiofaciocutaneous syndrome in which there is cardiac ... A number of genetic conditions are associated with heart defects including Down syndrome, Turner syndrome, and Marfan syndrome ... It is called hypoplastic left heart syndrome when it affects the left side of the heart and hypoplastic right heart syndrome ...
ATIC Alagille syndrome 2; 610205; NOTCH2 Alagille syndrome; 118450; JAG1 Aland Island eye disease; 300600; CACNA1F Albinism, ... AKAP9 Long QT syndrome-3; 603830; SCN5A Long QT syndrome-4; 600919; ANK2 Long QT syndrome-7; 170390; KCNJ2 Long QT syndrome-9; ... TGFBR2 Long QT syndrome 12; 612955; SNT1 Long QT syndrome 13; 613485; KCNJ5 Long QT syndrome-1; 192500; KCNQ1 Long QT syndrome- ... KRAS Noonan syndrome 4; 610733; SOS1 Noonan syndrome 5; 611553; RAF1 Noonan syndrome 6; 613224; NRAS Noonan-like syndrome with ...
These include: Alagille syndrome, an autosomal dominant disorder with a wide range of features and manifestations. Its five ... 2002). "Craniosynostosis in Alagille syndrome". American Journal of Medical Genetics. 112 (2): 176-80. doi:10.1002/ajmg.10608. ... Turnpenny, PD; Ellard, S (2011). "Alagille syndrome: Pathogenesis, diagnosis and management". European Journal of Human ... Rubinstein-Taybi syndrome, a mental retardation syndrome characterized by broad thumbs, facial abnormalities, and big toes ...
GeneReviews/NCBI/UW/NIH entry on Alagille syndrome OMIM entries on Alagille syndrome JAG1 protein, human at the US National ... McCright B, Lozier J, Gridley T (2002). "A mouse model of Alagille syndrome: Notch2 as a genetic modifier of Jag1 ... Notch signaling Alagille syndrome Autosomal dominant Haploinsufficiency Tetralogy of fallot In situ hybridization Conditional ... Piccoli DA, Spinner NB (2002). "Alagille syndrome and the Jagged1 gene". Semin. Liver Dis. 21 (4): 525-34. doi:10.1055/s-2001- ...
Zinn, Harry L.; Haller, J. O.; Kedia, Sanjay (1999). "Macromastia in a newborn with Alagille syndrome". Pediatric Radiology. 29 ... Aside from aromatase (as in aromatase excess syndrome), at least two other genetic mutations (one in PTEN) have been implicated ... Macromastia occurs in approximately half of women with aromatase excess syndrome (a condition of hyperestrogenism). ... syndrome: a novel phenotype maps to human chromosome 22q12.3-13.1". European Journal of Human Genetics. 18 (6): 662-667. doi: ...
Rand EB (1998). "The Genetic Basis of the Alagille Syndrome". Journal of Pediatric Gastroenterology & Nutrition. 26 (2): 234- ... Molecular genetics of Cohen syndrome Department of Medical Genetics, University of Helsinki. ...
Alagille syndrome), characterized by defects of the great vessels (pulmonary artery stenosis), heart (tetralogy of Fallot in 13 ... including Noonan syndrome, LEOPARD syndrome, Costello syndrome and cardiofaciocutaneous syndrome in which there is cardiac ... A number of genetic conditions are associated with heart defects including Down syndrome, Turner syndrome, and Marfan syndrome. ... It is called hypoplastic left heart syndrome when it affects the left side of the heart and hypoplastic right heart syndrome ...
For peripheral pulmonary artery stenosis in Alagille syndrome". Tex Heart Inst J. 25 (1): 79-82. PMC 325508 . PMID 9566070. ... Costello syndrome, Keutel syndrome, nasodigitoacoustic syndrome (Keipert syndrome), Noonan syndrome or Williams syndrome. It ... Peripheral pulmonary artery stenosis may occur as an isolated event or in association with Alagille syndrome, Berardinelli-Seip ...
... are a type of facies considered a symptom of Alagille syndrome. However it appears not to be specific but "a ... "Facial features in Alagille syndrome: Specific or cholestasis facies?". American Journal of Medical Genetics. 112 (2): 163-70. ... Is it specific for Alagille syndrome?". The Journal of Pediatrics. 103 (2): 205-8. doi:10.1016/S0022-3476(83)80345-X. PMID ...
JAG1: jagged 1 (Alagille syndrome). *JPH2: encoding protein Junctophilin 2. *KIZ: encoding protein Kizuna centrosomal protein ... PRNP: prion protein (p27-30) (Creutzfeldt-Jakob disease, Gerstmann-Strausler-Scheinker syndrome, fatal familial insomnia) ...
GeneReviews/NCBI/UW/NIH entry on Alagille syndrome OMIM entries on Alagille syndrome. ... NOTCH2 is associated with Alagille syndrome and Hajdu-Cheney syndrome. Notch 2 is a member of the notch family. Members of this ... "Screening for Alagille syndrome mutations in the JAG1 and NOTCH2 genes using denaturing high-performance liquid chromatography ... 2011). "Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss". Nature Genetics. 43 ( ...
NOTCH2 is associated with Alagille syndrome and Hajdu-Cheney syndrome. Notch signaling pathway Vardar D, North CL, Sanchez- ... "Screening for Alagille syndrome mutations in the JAG1 and NOTCH2 genes using denaturing high-performance liquid chromatography ... "Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss". Nature Genetics. 43 (4): 303- ...
Alagille syndrome Intrahepatic cholestasis of pregnancy Liver transplantation Shneider BL (2004). "Progressive intrahepatic ...
Jones EA, Clement-Jones M, Wilson DI (2000). "JAGGED1 expression in human embryos: correlation with the Alagille syndrome ... cause an X-linked mental retardation syndrome associated with aggressive outbursts, seizures, relative macrocephaly, central ...
Alagille syndrome, Down syndrome, Kenny-Caffey syndrome, Leber Hereditary Optic Neuropathy and linear nevus sebaceous syndrome ... Noonan syndrome and Alagille syndrome. Optic disc drusen are not related to Bruch membrane drusen of the retina which have been ... January 1997). "Ocular ultrasound in Alagille syndrome: a new sign". Ophthalmology. 104 (1): 79-85. doi:10.1016/s0161-6420(97) ... ISBN 0-07-137831-6. Online Mendelian Inheritance in Man (OMIM) Noonan syndrome -163950 Nischal KK, Hingorani M, Bentley CR, et ...
This phenotype resembles Alagille syndrome, a hallmark of which is mutations in Jagged1. Therefore, Hes-Notch interactions also ...
... and high whole blood manganese levels in Alagille's syndrome". Gastroenterology. 106 (4): 1068-71. PMID 8143974. Agency for ...
... has been excluded as a candidate gene in the cause of Alagille syndrome. GRCh38: Ensembl release 89: ENSG00000125844 - ...
... mice and absence of HEY2 mutations in patients with congenital heart defects or Alagille syndrome". Mamm. Genome. 15 (9): 711-6 ... Common variants of SCN5A, SCN10A, and HEY2 (this gene) are associated with Brugada syndrome. HEY2 has been shown to interact ... "Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac ...
... disappearing bile duct syndromes, Alagille's syndrome, cystic fibrosis, and biliary atresia. As a group, cholangiopathies ...
... zollinger-ellison syndrome MeSH C06.552.150.125 --- alagille syndrome MeSH C06.552.150.250 --- liver cirrhosis, biliary MeSH ... alagille syndrome MeSH C06.130.120.135.250.250 --- liver cirrhosis, biliary MeSH C06.130.120.200 --- cholangitis MeSH C06.130. ... gardner syndrome MeSH C06.405.469.578.750 --- peutz-jeghers syndrome MeSH C06.405.469.600 --- jejunal diseases MeSH C06.405. ... postgastrectomy syndromes MeSH C06.405.748.630.310 --- dumping syndrome MeSH C06.405.748.789 --- stomach neoplasms MeSH C06.405 ...
Albright's hereditary osteodystrophy Arterial tortuosity syndrome Adenosine deaminase deficiency Alagille syndrome Fatal ... Alagille syndrome) JPH2: encoding protein Junctophilin 2 KIZ: encoding protein Kizuna centrosomal protein Kua-UEV: LIME1: ... Hallervorden-Spatz syndrome) PKIG: encoding protein cAMP-dependent protein kinase inhibitor gamma PLAGL2: encoding protein Zinc ... Waardenburg syndrome G-banding ideograms of human chromosome 20 "Human Genome Assembly GRCh38 - Genome Reference Consortium". ...
There are also many pediatric liver diseases, including biliary atresia, alpha-1 antitrypsin deficiency, alagille syndrome, ... Budd-Chiari syndrome is a condition caused by blockage of the hepatic veins (including thrombosis) that drain the liver. It ... "Budd-Chiari syndrome in Sweden: epidemiology, clinical characteristics and survival - an 18-year experience". Liver ...
Other congenital malformations of liver Accessory liver Alagille's syndrome (Q45) Other congenital malformations of digestive ... De Lange syndrome (ILDS Q87.170) Dubowitz syndrome Noonan syndrome Prader-Willi syndrome Robinow-Silverman-Smith syndrome ... Cryptophthalmos syndrome Cyclopia Goldenhar syndrome Moebius syndrome oro-facial-digital syndrome Robin syndrome Whistling face ... Seckel syndrome Smith-Lemli-Opitz syndrome Sjögren-Larsson syndrome (ILDS Q87.136) (Q87.2) Congenital malformation syndromes ...
... alagille syndrome MeSH C16.131.077.095 --- angelman syndrome MeSH C16.131.077.112 --- bardet-biedl syndrome MeSH C16.131. ... branchio-oto-renal syndrome MeSH C16.131.260.190 --- cri-du-chat syndrome MeSH C16.131.260.210 --- de lange syndrome MeSH ... branchio-oto-renal syndrome MeSH C16.320.180.190 --- cri-du-chat syndrome MeSH C16.320.180.210 --- de lange syndrome MeSH ... cockayne syndrome MeSH C16.131.077.262 --- cri-du-chat syndrome MeSH C16.131.077.272 --- de lange syndrome MeSH C16.131.077.327 ...
... dumping syndrome, excessive scarring, and rarely, achalasia.[10] Surgical procedures sometimes fail over time, requiring a ... Complications from surgical procedures to correct a hiatal hernia may include gas bloat syndrome, dysphagia (trouble swallowing ...
Important Articles on Alagille syndrome. 1. Alagille syndrome: spectrum of clinical presentation in India. http://www.ncbi.nlm. ... What is Alagille syndrome?. It is a Genetic disorder(JAG 1 gene) also known as arteriohepatic dysplasia.Children usually have a ... Does child with Alagille syndrome have vitamin deficiency?. Problems with fat digestion and absorption may lead to deficiency ... How to diagnose Alagille syndrome?. Diagnosis is often based on the medical history, physical examination, and blood tests. ...
Alagille syndrome is an autosomal dominant disorder with high penetrance but variable expressivity. Alagille syndrome 1 (ALGS1 ... Approximately 95% of patients with Alagille syndrome have a mutation in the JAG1 gene. About 2% of Alagille patients have a ... Alagille syndrome 2 (ALGS2; MIM 610205) is caused by mutations in NOTCH2, which encodes a transmembrane Notch receptor. ... Alagille syndrome is an autosomal dominant disorder with high penetrance but variable expressivity.read more ...
A total of 16 patients were identified: 7 had Williams syndrome, 6 had Alagille syndrome, and 3 had no identifiable syndrome. ... A total of 16 patients were identified: 7 had Williams syndrome, 6 had Alagille syndrome, and 3 had no identifiable syndrome. ... A total of 16 patients were identified: 7 had Williams syndrome, 6 had Alagille syndrome, and 3 had no identifiable syndrome. ... A total of 16 patients were identified: 7 had Williams syndrome, 6 had Alagille syndrome, and 3 had no identifiable syndrome. ...
Evaluation of risk for atherosclerosis in Alagille syndrome and progressive familial intrahepatic cholestasis: two congenital ... Alagille syndrome and biliary atresia [13]. We would like to emphasize that high dose Vitamin D supplementation therapy needs ...
... and other parts of the body.One of the major features of Alagille syndrome is liver damage caused by abnormalities in the bile ... Alagille syndrome is a genetic disorder that can affect the liver, heart, ... mutations in the JAG1 gene cause Alagille syndrome. Another 7 percent of individuals with Alagille syndrome have small ... medlineplus.gov/genetics/condition/alagille-syndrome/ Alagille syndrome. ...
Information about Alagille syndrome causes, symptoms, diagnosis and treatment, provided by Cincinnati Childrens Hospital ... Diagnosis of Alagille Syndrome Show A diagnosis of Alagille syndrome may be made based on genetic testing, or by having certain ... Treatment for Alagille Syndrome Show There is no cure for Alagille syndrome. Management of the disorder is aimed at preventing ... Alagille Syndrome Alagille syndrome is a rare, inherited disorder. It can affect the liver, heart, eyes, bones, kidneys and ...
Alagille Syndrome Alliance message board GeneReviews/NCBI/UW/NIH entry on Alagille syndrome OMIM entries on Alagille syndrome ... Alagille syndrome, Alagille-Watson syndrome or ALGS, is an autosomal dominant genetic disorder that affects the liver, heart, ... "Alagille Syndrome". WSJ.com. WSJ. Retrieved November 9, 2016. Official Website for the Alagille Syndrome Alliance Official ... and the estimated prevalence of Alagille syndrome is 1 in every 100,000 live births. It is named for Daniel Alagille. The ...
Describes Alagille syndrome, a rare, inherited disorder that affects the liver. Covers the causes, symptoms, diagnosis, ... Alagille Syndrome. View or Print All Sections Definition & Facts Alagille syndrome is a genetic disorder that may affect many ... The most common signs and symptoms of Alagille syndrome are related to the liver. Alagille syndrome may also affect other parts ... A person with Alagille syndrome has fewer than the normal number of small bile ducts inside the liver. As bile builds up in the ...
... and complications of Alagille syndrome with medicines and surgery. ... Treatment for Alagille Syndrome. How do doctors treat Alagille syndrome?. Doctors may refer people with Alagille syndrome to a ... Can I prevent Alagille syndrome?. Experts have not yet found a way to prevent Alagille syndrome. People with Alagille syndrome ... How do doctors treat the complications of Alagille syndrome?. Liver complications. If Alagille syndrome leads to cirrhosis and ...
A new mouse model of Alagille syndrome. *Iain Dickson Nature Reviews Gastroenterology & Hepatology volume 15, page4(2018)Cite ... Alagille syndrome is a genetic disorder characterized by severe liver and heart abnormalities, and ocular, vertebral and ... in which bile duct development is disrupted and most features of Alagille syndrome are reproduced. Using this model, the ... Mouse model of Alagille syndrome and mechanisms of Jagged1 missense mutations. Gastroenterology http://dx.doi.org/10.1053/j. ...
Characterization of Pulmonary Artery Stenoses in Alagille Syndrome - a Medical Record Review. *Alagille Syndrome ... Evaluation of LUM001 in the Reduction of Pruritus in Alagille Syndrome. *Alagille Syndrome ... Positional Cloning of the Gene(s) Responsible for Alagille Syndrome. *Alagille Syndrome ... Randomized Drug Withdrawal Period to Evaluate Safety and Efficacy in Children With Alagille Syndrome. *Alagille Syndrome ...
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Alagille syndrome is a rare liver disorder that can affect many major organs in the body. Learn more from Boston Childrens ... Alagille Syndrome. What is Alagille syndrome?. The syndrome is usually diagnosed during infancy or early childhood. Alagille ... What causes Alagille syndrome?. Alagille syndrome is caused by a gene mutation that can pass from parent to child. Between 30 ... What are the symptoms of Alagille syndrome?. The symptoms of Alagille syndrome vary from child to child and are more severe in ...
Alagille syndrome (ALGS), also known as arteriohepatic dysplasia, is a rare autosomal dominant genetic disorder caused by ... Alagille syndrome is an autosomal dominant disorder with variable expression.. *Alagille syndrome and associated abnormalities ... Alagille D, Estrada A, Hadchouel M, et al. (1987) Syndromic paucity of interlobular bile ducts (Alagille syndrome or ... Alagille syndrome is most often caused by a mutation, or defect, in the JAGGED1 (JAG1) or NOTCH2 receptor gene. ...
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Alagille syndrome is an autosomal dominant inherited disorder associated with liver, heart, eye and skeletal abnormalities, and ... What is Alagille syndrome?. Alagille syndrome - also known as Alagille-Watson syndrome, syndromic bile duct paucity and ... Frequently asked questions about Alagille syndrome. Is Alagille syndrome always inherited?. No. In about half of the Alagille ... The pancreas and Alagille syndrome. It is well-documented that Alagille syndrome affects multiple organs, such as the liver, ...
AHD, Alagille syndrome 1, Alagilles syndrome, Alagille-Watson syndrome, ALGS, ALGS1, anomalies of the optic disc, aortic ... Many people with Alagille syndrome have poor growth and developmental delays.. *Cognitive: People with Alagille syndrome may ... Alagille Syndrome Alliance. .. *Alessandro G, Incerti M, Andreani M. Alagille syndrome: prenatal sonographic findings. J Clin ... About 30% of cases of Alagille syndrome, however, have unknown causes. In about 30-50% of cases of Alagille syndrome, a person ...
... in children with Alagille syndrome (AGS) in comparison with a normative population and other chronic diseases, and also to ... OBJECTIVES: The aim of the study was to assess health-related quality of life (HRQOL) in children with Alagille syndrome (AGS) ...
Alagille Syndrome. Alagille syndrome is a rare genetic disorder that is caused by hereditary or spontaneous mutations in JAG1 ... Alagille syndrome is an inherited disease in which the patient has fewer than the normal number of bile ducts leading to ... He is a victim of serious Alagille Syndrome, which causes him to itch uncontrollably. This disease can turn life threatening ... Approximately 75% of the children diagnosed with Alagille syndrome live to 20 years of age; deaths most often is caused by ...
Eighty five percent of patients with Alagille Syndrome have progressive loss of bile ducts in the liver and narrowing of ... In addition to defects in the biliary system, newborns with Alagille Syndrome have defects in their cardiovascular system (most ... Alagille Syndrome, sometimes called arteriohepatic dysplasia, is an autosomal dominant disease with highly variable ... The Alagille Syndrome Alliance (USA). Alagille Syndrome Alliance. [Support Groups]. The Alagille Syndrome Alliance is a ...
Alagille syndrome is a rare, genetic condition. It can affect different parts of the body including the liver, heart, kidneys, ... How is Alagille syndrome diagnosed?. If your child has some of the features of Alagille syndrome there are a number of tests ... How is Alagille syndrome treated?. There is no cure for Alagille syndrome but there are treatments that can deal with the ... What are the effects of Alagille syndrome?. Although some individuals with Alagille syndrome wont have any issues with their ...
Alagille syndrome), Authors: Michèle Meunier-Rotival, Catherine Driancourt, Julie Boyer-Di Ponio. Published in: Atlas Genet ... Alagille syndrome (AGS). Disease. syndrome associating 5 major features (complete syndrome) : paucity of interlobular bile ... Alagille syndrome and deletion of 20p.. Anad F, Burn J, Matthews D, Cross I, Davison BC, Mueller R, Sands M, Lillington DM, ... JAG1 jagged 1 (Alagille syndrome). Written. 2005-10. Michèle Meunier-Rotival, Catherine Driancourt, Julie Boyer-Di Ponio. ...
For most of his life, Alejandro was in and out of the hospital due to complications from Alagille syndrome. But a year after a ... Alagille Syndrome and Liver Transplant: Alejandros Story. Published on Mar 09, 2018 ... The liver transplant eliminated many of the most critical symptoms of his Alagille syndrome, but he will always have the ... It appeared that Alejandro had Alagille syndrome, a genetic condition associated with liver, heart and eye problems and ...
Was your child recently diagnosed with Alagilles Syndrome? Learn about the symptoms, diagnosis and treatment for this rare ... Alagilles Syndrome Symptoms and Treatment Options. What Is Alagilles Syndrome?. In Alagilles syndrome, also known as " ... Alagilles Syndrome Symptoms in Children. Alagilles syndrome symptoms can range from mild to severe; a person with Alagilles ... Alagilles Syndrome Treatment. There is no cure for Alagilles syndrome, but the symptoms can usually be managed without ...
... researchers at Karolinska Institutet have discovered that the liver disease part of the syndrome is caused by specific ... Serious liver and heart problems can affect children with Alagille Syndrome early in life. While there is as yet no cure, ... Children with Alagille Syndrome have malformed bile ducts. Published 2017-11-21 12:54. Updated 2017-11-21 13:46Denna sida på ... "Mouse Model of Alagille Syndrome and Mechanisms of Jagged1 Missense Mutations". Emma Rachel Andersson. Indira V Chivukula, ...
  • Newborns with Alagille syndrome may have jaundice , a yellowish tint of the eyes and skin, and poor growth during their first few months. (childrenshospital.org)
  • A child who is born with Alagille syndrome will experience jaundice (yellowing of the skin and whites of the eyes), pale, loose stool and failure to thrive . (rileychildrens.org)
  • Other presentations of Alagille's syndrome include an unusual butterfly shape of one or more of the bones of the spinal column (visible on an x-ray), certain eye defects (such as posterior embryotoxon and pigmentary retinopathy), and narrowed pulmonary arteries that can contribute to increased pressure on the right heart valves. (wikipedia.org)
  • Some individuals who inherit a mutation have severe Alagille syndrome, involving heart and liver disease, while others experience only minor manifestations, such as posterior embryotoxon or characteristic facial features. (chop.edu)
  • A ring on the cornea, called a posterior embryotoxon, is a classic sign of the syndrome. (cedars-sinai.org)
  • Among the Alagille syndrome affected children, 1/3rd of them inherit the mutation in Jagged 1, from a parent. (symptomstreatment.org)
  • 2013. Alagille Syndrome: A New Missense Mutation Detected by Whole-Exome Sequencingin a Case Previously Found to Be Negativeby DHPLC and MLPA. (med-expert.com.ua)
  • Netherton syndrome, a rare skin disease caused by a single genetic mutation, is exacerbated by the presence of two common Staphylococcal bacteria living on human skin, one of which was previously thought to only offer protective properties, report University of California San Diego School of Medicine researchers. (news-medical.net)
  • Some signs of Alagille syndrome typically don't cause health problems or require treatment. (nih.gov)
  • If you have one parent with Alagille syndrome, you have a 50% chance of developing the condition. (cedars-sinai.org)
  • Berniczei-Royko A, Chałas R, Mitura I, Nagy K, Prussak E. Medical and dental management of Alagille syndrome: a review. (medlineplus.gov)
  • 2010. Medical Management of Alagille Syndrome. (med-expert.com.ua)
  • Renal involvement and the role of Notch signalling in Alagille syndrome. (springer.com)