Chromosomes, Human, Pair 15
snRNP Core Proteins
Ribonucleoproteins, Small Nuclear
In Situ Hybridization, Fluorescence
Methyl-CpG-Binding Protein 2
In vivo nuclease hypersensitivity studies reveal multiple sites of parental origin-dependent differential chromatin conformation in the 150 kb SNRPN transcription unit. (1/228)Human chromosome region 15q11-q13 contains a cluster of oppositely imprinted genes. Loss of the paternal or the maternal alleles by deletion of the region or by uniparental disomy 15 results in Prader-Willi syndrome (PWS) or Angelman syndrome (AS), respectively. Hence, the two phenotypically distinct neurodevelopmental disorders are caused by the lack of products of imprinted genes. Subsets of PWS and AS patients exhibit 'imprinting mutations', such as small microdeletions within the 5' region of the small nuclear ribonucleoprotein polypeptide N ( SNRPN ) transcription unit which affect the transcriptional activity and methylation status of distant imprinted genes throughout 15q11-q13 in cis. To elucidate the mechanism of these long-range effects, we have analyzed the chromatin structure of the 150 kb SNRPN transcription unit for DNase I- and Msp I-hypersensitive sites. By using an in vivo approach on lymphoblastoid cell lines from PWS and AS individuals, we discovered that the SNRPN exon 1 is flanked by prominent hypersensitive sites on the paternal allele, but is completely inaccessible to nucleases on the maternal allele. In contrast, we identified several regions of increased nuclease hypersensitivity on the maternal allele, one of which coincides with the AS minimal microdeletion region and another lies in intron 1 immediately downstream of the paternal-specific hypersensitive sites. At several sites, parental origin-specific nuclease hypersensitivity was found to be correlated with hypermethylation on the allele contributed by the other parent. The differential parental origin-dependent chromatin conformations might govern access of regulatory protein complexes and/or RNAs which could mediate interaction of the region with other genes. (+info)
Genomic imprinting: implications for human disease. (2/228)Genomic imprinting refers to an epigenetic marking of genes that results in monoallelic expression. This parent-of-origin dependent phenomenon is a notable exception to the laws of Mendelian genetics. Imprinted genes are intricately involved in fetal and behavioral development. Consequently, abnormal expression of these genes results in numerous human genetic disorders including carcinogenesis. This paper reviews genomic imprinting and its role in human disease. Additional information about imprinted genes can be found on the Genomic Imprinting Website at http://www.geneimprint.com. (+info)
Parental view of epilepsy in Angelman syndrome: a questionnaire study. (3/228)PURPOSE: To explore parents' opinions and concerns about seizures, anticonvulsants, and the effect of treatment in children with Angelman syndrome. DESIGN: A postal questionnaire was sent to members of one of the UK lay groups for Angelman syndrome (ASSERT) who had a child affected by Angelman syndrome. The questionnaire requested general medical information and information about the epilepsy, its treatment, and treatment responses. RESULTS: One hundred and fifty questionnaires were sent out with an ASSERT routine mailing and 78 completed questionnaires were returned. Forty three patients were boys and 35 were girls; ages ranged from 1.7 to 25 years (mean 7.5 years). The overall general clinical and cytogenetic data were mostly consistent with previous reports. Epilepsy was reported in 68 children, most of whom had a detectable cytogenetic deletion. The most common seizure types reported by the families were absence seizures, tonic clonic seizures, drop attacks, and myoclonic seizures; in four patients only febrile seizures occurred. The age at onset of the seizures was < 2 years in more than half of the patients. Anti-epileptic drug treatment with valproate (VPA), clonazepam (CZP), and lamotrigine (LTG) as monotherapy or a combination of VPA and CZP or VPA and LTG was more often viewed favourably and considered effective with fewer side effects on the child's behaviour and alertness, versus more frequent adverse effects and increased frequency and severity of seizures with carbamazepine (CBZ) and vigabatrin (VGB) in monotherapy or in combination with other anti-epileptic drugs. Seizures did tend to improve with age but were still present and disabling at older ages. CONCLUSIONS: This is the first study to record parents' opinions about seizures, anti-epileptic drugs, and treatment responses in children with Angelman syndrome, and it is one of the largest series on epilepsy and Angelman syndrome to be reported to date. (+info)
Phenotype-genotype correlation in 20 deletion and 20 non-deletion Angelman syndrome patients. (4/228)Angelman syndrome (AS) is a neurodevelopmental disorder caused by the absence of a maternal contribution to chromosome 15q11-q13. There are four classes of AS according to molecular or cytogenetic status: maternal microdeletion of 15q11-q13 (approximately 70% of AS patients); uniparental disomy (UPD); defects in a putative imprinting centre (IM); the fourth includes 20-30% of AS individuals with biparental inheritance and a normal pattern of allelic methylation in 15q11-q13. Mutations of UBE3A have recently been identified as causing AS in the latter group. Few studies have investigated the phenotypic differences between these classes. We compared 20 non-deletion to 20 age-matched deletion patients and found significant phenotypic differences between the two groups. The more severe phenotype in the deletion group may suggest a contiguous gene syndrome. (+info)
Large genomic duplicons map to sites of instability in the Prader-Willi/Angelman syndrome chromosome region (15q11-q13). (5/228)The most common etiology for Prader-Willi syndrome and Angelman syndrome is de novo interstitial deletion of chromosome 15q11-q13. Deletions and other recurrent rearrangements of this region involve four common 'hotspots' for breakage, termed breakpoints 1-4 (BP1-BP4). Construction of an approximately 4 Mb YAC contig of this region identified multiple sequence tagged sites (STSs) present at both BP2 and BP3, suggestive of a genomic duplication event. Interphase FISH studies demonstrated three to five copies on 15q11-q13, one copy on 16p11.1-p11.2 and one copy on 15q24 in normal controls, while analysis on two Class I deletion patients showed loss of approximately three signals at 15q11-q13 on one homolog. Multiple FISH signals were also observed at regions orthologous to both human chromosomes 15 and 16 in non-human primates, including Old World monkeys, suggesting that duplication of this region may have occurred approximately 20 million years ago. A BAC/PAC contig for the duplicated genomic segment (duplicon) demonstrated a size of approximately 400 kb. Surprisingly, the duplicon was found to contain at least seven different expressed sequence tags representing multiple genes/pseudogenes. Sequence comparison of STSs amplified from YAC clones uniquely mapped to BP2 or BP3 showed two different copies of the duplicon within BP3, while BP2 comprised a single copy. The orientation of BP2 and BP3 are inverted relative to each other, whereas the two copies within BP3 are in tandem. The presence of large duplicated segments on chromosome 15q11-q13 provides a mechanism for homologous unequal recombination events that may mediate the frequent rearrangements observed for this chromosome. (+info)
Chromosome breakage in the Prader-Willi and Angelman syndromes involves recombination between large, transcribed repeats at proximal and distal breakpoints. (6/228)Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct neurobehavioral disorders that most often arise from a 4-Mb deletion of chromosome 15q11-q13 during paternal or maternal gametogenesis, respectively. At a de novo frequency of approximately.67-1/10,000 births, these deletions represent a common structural chromosome change in the human genome. To elucidate the mechanism underlying these events, we characterized the regions that contain two proximal breakpoint clusters and a distal cluster. Novel DNA sequences potentially associated with the breakpoints were positionally cloned from YACs within or near these regions. Analyses of rodent-human somatic-cell hybrids, YAC contigs, and FISH of normal or rearranged chromosomes 15 identified duplicated sequences (the END repeats) at or near the breakpoints. The END-repeat units are derived from large genomic duplications of a novel gene (HERC2), many copies of which are transcriptionally active in germline tissues. One of five PWS/AS patients analyzed to date has an identifiable, rearranged HERC2 transcript derived from the deletion event. We postulate that the END repeats flanking 15q11-q13 mediate homologous recombination resulting in deletion. Furthermore, we propose that active transcription of these repeats in male and female germ cells may facilitate the homologous recombination process. (+info)
Angelman syndrome resulting from UBE3A mutations in 14 patients from eight families: clinical manifestations and genetic counselling. (7/228)Angelman syndrome (AS) is a neurological disorder with a heterogeneous genetic aetiology. It most frequently results from a de novo interstitial deletion in the 15q11-q13 region, but in a few cases it is caused by paternal uniparental disomy (UPD) or an imprinting mutation. The remaining 20 to 30% of AS patients exhibit biparental inheritance and a normal pattern of allelic methylation in the 15q11-q13 region. In this latter group, mutations in the UBE3A gene have recently been shown to be a cause of AS. Here we describe the phenotypic expression in 14 AS cases involving eight UBE3A mutations. These comprise 11 familial cases from five families and three sporadic cases. Subtle differences from the typical phenotype of AS were found. Consistent manifestations were psychomotor delay, a happy disposition, a hyperexcitable personality, EEG abnormalities, and mental retardation with severe speech impairment. The other main manifestations of AS, ataxia, epilepsy, and microcephaly, were either milder or absent in various combinations among the patients. In addition, myoclonus of cortical origin was frequently observed with severe fits inducing myoclonic seizures. The majority of the patients were overweight. This study showed that ataxia, myoclonus, EEG abnormalities, speech impairment, characteristic behavioural phenotype, and abnormal head circumference are attributable to a deficiency in the maternally inherited UBE3A allele. Furthermore, analysis of mutation transmission showed an unexpectedly high rate of somatic mosaicism in normal carriers. These data have important consequences for genetic counselling. (+info)
A transgene insertion creating a heritable chromosome deletion mouse model of Prader-Willi and angelman syndromes. (8/228)Prader-Willi syndrome (PWS) and Angelman syndrome (AS) result from the loss of function of imprinted genes in human chromosome 15q11-q13. The central part of mouse chromosome 7 is homologous to human 15q11-q13, with conservation of both gene order and imprinted features. We report here the characterization of a transgene insertion (Epstein-Barr virus Latent Membrane Protein 2A, LMP2A) into mouse chromosome 7C, which has resulted in mouse models for PWS and AS dependent on the sex of the transmitting parent. Epigenotype (allelic expression and DNA methylation) and fluorescence in situ hybridization analyses indicate that the transgene-induced mutation has generated a complete deletion of the PWS/AS-homologous region but has not deleted flanking loci. Because the intact chromosome 7, opposite the deleted homolog, maintains the correct imprint in somatic cells of PWS and AS mice and establishes the correct imprint in male and female germ cells of AS mice, homologous association and replication asynchrony are not part of the imprinting mechanism. This heritable-deletion mouse model will be particularly useful for the identification of the etiological genes and mechanisms, phenotypic basis, and investigation of therapeutic approaches for PWS. (+info)
The main symptoms of AS include:
1. Developmental delay: Children with AS typically experience delays in reaching milestones such as sitting, standing, and walking.
2. Intellectual disability: Individuals with AS often have low IQ scores and may have difficulty with language skills, memory, and problem-solving.
3. Happy demeanor: People with AS are known to have a happy, outgoing, and sociable personality.
4. Speech and language difficulties: Individuals with AS may have trouble articulating words and sentences.
5. Motor skills problems: They may experience difficulty with coordination, balance, and fine motor skills.
6. Seizures: About 10% of individuals with AS experience seizures, usually in the form of atonic seizures (also known as drop attacks).
7. Sleep disturbances: Many people with AS have sleep problems, including insomnia and restlessness.
8. Behavioral issues: Some individuals with AS may exhibit behavioral challenges such as hyperactivity, impulsivity, and anxiety.
9. Vision problems: Some people with AS may experience vision difficulties, including strabismus (crossed eyes) and nystagmus (involuntary eye movements).
10. Feeding difficulties: Some individuals with AS may have trouble feeding themselves or experiencing gastrointestinal issues.
There is no cure for Angelman Syndrome, but various therapies can help manage the symptoms and improve the quality of life for individuals affected by the disorder. These may include physical therapy, occupational therapy, speech therapy, and behavioral interventions. Medications such as anticonvulsants and mood stabilizers may also be prescribed to manage seizures and other symptoms.
PWS is characterized by a range of physical, cognitive, and behavioral symptoms, including:
1. Delayed growth and development: Individuals with PWS often have slowed growth before birth and may be born with low birth weight. They may also experience delayed puberty and short stature compared to their peers.
2. Intellectual disability: Many individuals with PWS have intellectual disability, which can range from mild to severe.
3. Behavioral problems: PWS is often associated with behavioral challenges, such as attention deficit hyperactivity disorder (ADHD), anxiety, and obsessive-compulsive disorder (OCD).
4. Feeding and eating difficulties: Individuals with PWS may have difficulty feeding and swallowing, which can lead to nutritional deficiencies and other health problems. They may also experience a condition called "hyperphagia," which is characterized by excessive hunger and overeating.
5. Sleep disturbances: PWS is often associated with sleep disturbances, such as insomnia and restlessness.
6. Short stature: Individuals with PWS tend to be shorter than their peers, with an average adult height of around 4 feet 10 inches (147 cm).
7. Body composition: PWS is often characterized by a high percentage of body fat, which can increase the risk of obesity and other health problems.
8. Hormonal imbalances: PWS can disrupt the balance of hormones in the body, leading to issues such as hypogonadism (low testosterone levels) and hypothyroidism (underactive thyroid).
9. Dental problems: Individuals with PWS are at increased risk of dental problems, including tooth decay and gum disease.
10. Vision and hearing problems: Some individuals with PWS may experience vision and hearing problems, such as nearsightedness, farsightedness, and hearing loss.
It's important to note that every individual with PWS is unique, and not all will experience all of these symptoms. Additionally, the severity of the disorder can vary widely from person to person. With proper medical care and management, however, many individuals with PWS can lead fulfilling and productive lives.
Examples of syndromes include:
1. Down syndrome: A genetic disorder caused by an extra copy of chromosome 21 that affects intellectual and physical development.
2. Turner syndrome: A genetic disorder caused by a missing or partially deleted X chromosome that affects physical growth and development in females.
3. Marfan syndrome: A genetic disorder affecting the body's connective tissue, causing tall stature, long limbs, and cardiovascular problems.
4. Alzheimer's disease: A neurodegenerative disorder characterized by memory loss, confusion, and changes in personality and behavior.
5. Parkinson's disease: A neurological disorder characterized by tremors, rigidity, and difficulty with movement.
6. Klinefelter syndrome: A genetic disorder caused by an extra X chromosome in males, leading to infertility and other physical characteristics.
7. Williams syndrome: A rare genetic disorder caused by a deletion of genetic material on chromosome 7, characterized by cardiovascular problems, developmental delays, and a distinctive facial appearance.
8. Fragile X syndrome: The most common form of inherited intellectual disability, caused by an expansion of a specific gene on the X chromosome.
9. Prader-Willi syndrome: A genetic disorder caused by a defect in the hypothalamus, leading to problems with appetite regulation and obesity.
10. Sjogren's syndrome: An autoimmune disorder that affects the glands that produce tears and saliva, causing dry eyes and mouth.
Syndromes can be diagnosed through a combination of physical examination, medical history, laboratory tests, and imaging studies. Treatment for a syndrome depends on the underlying cause and the specific symptoms and signs presented by the patient.
Types of Uniparental Disomy:
There are two types of UPD:
1. Uniparental disomy 22 (UPD(22): This type is caused by a deletion of one copy of chromosome 22, resulting in an individual having only one copy of the entire chromosome or a portion of it.
2. Uniparental disomy 15 (UPD(15): This type is caused by a deletion of one copy of chromosome 15, resulting in an individual having only one copy of the entire chromosome or a portion of it.
Causes and Symptoms:
The causes of UPD are not well understood, but it is believed that it may be caused by errors during cell division or the fusion of cells. Symptoms of UPD can vary depending on the location and size of the deleted chromosome material, but they may include:
1. Developmental delays
2. Intellectual disability
3. Speech and language difficulties
4. Behavioral problems
5. Dysmorphic features (physical abnormalities)
6. Congenital anomalies (birth defects)
7. Increased risk of infections and autoimmune disorders
8. Short stature
9. Skeletal abnormalities
10. Cardiac defects
Diagnosis and Treatment:
The diagnosis of UPD is based on a combination of clinical features, chromosomal analysis, and molecular genetic testing. Treatment for UPD is focused on managing the symptoms and addressing any underlying medical issues. This may include:
1. Speech and language therapy
2. Occupational therapy
3. Physical therapy
4. Medications to manage behavioral problems or seizures
5. Surgery to correct physical abnormalities or congenital anomalies
6. Infection prophylaxis (to prevent infections)
7. Immunoglobulin replacement therapy (to boost the immune system)
8. Antibiotics (to treat infections)
9. Cardiac management (to address any heart defects)
UPD can be diagnosed prenatally using chorionic villus sampling or amniocentesis, which involve analyzing a sample of cells from the placenta or amniotic fluid. This allows parents to prepare for the possibility of a child with UPD and to make informed decisions about their pregnancy.
Counseling and Psychosocial Support:
UPD can have significant psychosocial implications for families, including anxiety, depression, and social isolation. It is essential to provide counseling and psychosocial support to parents and families to help them cope with the diagnosis and manage the challenges of raising a child with UPD.
UPD can be inherited in an autosomal dominant manner, meaning that a single copy of the mutated gene is enough to cause the condition. Genetic counseling can help families understand the risk of recurrence and make informed decisions about their reproductive options.
Rehabilitation and Therapy:
Children with UPD may require ongoing therapy and rehabilitation to address physical, cognitive, and behavioral challenges. This may include occupational therapy, speech therapy, and physical therapy.
Parental Support Groups:
Support groups for parents of children with UPD can provide a valuable source of information, emotional support, and practical advice. These groups can help families connect with others who are facing similar challenges and can help them feel less isolated and more empowered to navigate the complexities of raising a child with UPD.
In conclusion, the diagnosis of UPD can have significant implications for individuals and families. By understanding the causes, symptoms, diagnosis, treatment, and management options, healthcare providers can provide comprehensive care and support to those affected by this condition. Additionally, counseling, psychosocial support, genetic counseling, rehabilitation, and therapy can all play important roles in helping families navigate the challenges of UPD and improving the quality of life for individuals with this condition.
The main features of BWS include:
1. Macroglossia (enlarged tongue): This is the most common feature of BWS, and it can cause difficulty with speaking and breathing.
2. Protruding ears: Children with BWS often have large ears that stick out from their head.
3. Omphalocele: This is a birth defect in which the intestines or other organs protrude through the navel.
4. Hydrocephalus: This is a build-up of fluid in the brain, which can cause increased pressure and enlargement of the head.
5. Polyhydramnios: This is a condition in which there is too much amniotic fluid surrounding the fetus during pregnancy.
6. Imperforate anus: This is a birth defect in which the anus is not properly formed, leading to difficulty with bowel movements.
7. Developmental delays: Children with BWS may experience delays in reaching developmental milestones, such as sitting, standing, and walking.
8. Intellectual disability: Some individuals with BWS may have mild to moderate intellectual disability.
9. Increased risk of cancer: Individuals with BWS have an increased risk of developing certain types of cancer, particularly Wilms tumor (a type of kidney cancer) and hepatoblastoma (a type of liver cancer).
There is no cure for Beckwith-Wiedemann Syndrome, but various treatments can be used to manage the associated symptoms and prevent complications. These may include surgery, physical therapy, speech therapy, and medication. With appropriate medical care and support, individuals with BWS can lead fulfilling lives.
Some common effects of chromosomal deletions include:
1. Genetic disorders: Chromosomal deletions can lead to a variety of genetic disorders, such as Down syndrome, which is caused by a deletion of a portion of chromosome 21. Other examples include Prader-Willi syndrome (deletion of chromosome 15), and Williams syndrome (deletion of chromosome 7).
2. Birth defects: Chromosomal deletions can increase the risk of birth defects, such as heart defects, cleft palate, and limb abnormalities.
3. Developmental delays: Children with chromosomal deletions may experience developmental delays, learning disabilities, and intellectual disability.
4. Increased cancer risk: Some chromosomal deletions can increase the risk of developing certain types of cancer, such as chronic myelogenous leukemia (CML) and breast cancer.
5. Reproductive problems: Chromosomal deletions can lead to reproductive problems, such as infertility or recurrent miscarriage.
Chromosomal deletions can be diagnosed through a variety of techniques, including karyotyping (examination of the chromosomes), fluorescence in situ hybridization (FISH), and microarray analysis. Treatment options for chromosomal deletions depend on the specific effects of the deletion and may include medication, surgery, or other forms of therapy.
There are various causes of intellectual disability, including:
1. Genetic disorders, such as Down syndrome, Fragile X syndrome, and Turner syndrome.
2. Congenital conditions, such as microcephaly and hydrocephalus.
3. Brain injuries, such as traumatic brain injury or hypoxic-ischemic injury.
4. Infections, such as meningitis or encephalitis.
5. Nutritional deficiencies, such as iron deficiency or iodine deficiency.
Intellectual disability can result in a range of cognitive and functional impairments, including:
1. Delayed language development and difficulty with communication.
2. Difficulty with social interactions and adapting to new situations.
3. Limited problem-solving skills and difficulty with abstract thinking.
4. Slow learning and memory difficulties.
5. Difficulty with fine motor skills and coordination.
There is no cure for intellectual disability, but early identification and intervention can significantly improve outcomes. Treatment options may include:
1. Special education programs tailored to the individual's needs.
2. Behavioral therapies, such as applied behavior analysis (ABA) and positive behavior support (PBS).
3. Speech and language therapy.
4. Occupational therapy to improve daily living skills.
5. Medications to manage associated behaviors or symptoms.
It is essential to recognize that intellectual disability is a lifelong condition, but with appropriate support and resources, individuals with ID can lead fulfilling lives and reach their full potential.
* Genetic mutations or chromosomal abnormalities
* Infections during pregnancy, such as rubella or toxoplasmosis
* Exposure to certain medications or chemicals during pregnancy
* Maternal malnutrition or poor nutrition during pregnancy
* Certain medical conditions, such as hypothyroidism or anemia.
Microcephaly can be diagnosed by measuring the baby's head circumference and comparing it to established norms for their age and gender. Other signs of microcephaly may include:
* A small, misshapen head
* Small eyes and ears
* Developmental delays or intellectual disability
* Seizures or other neurological problems
* Difficulty feeding or sucking
There is no cure for microcephaly, but early diagnosis and intervention can help manage the associated symptoms and improve quality of life. Treatment may include:
* Monitoring growth and development
* Physical therapy to improve muscle tone and coordination
* Occupational therapy to develop fine motor skills and coordination
* Speech therapy to improve communication skills
* Medication to control seizures or other neurological problems.
In some cases, microcephaly may be associated with other medical conditions, such as intellectual disability, autism, or vision or hearing loss. It is important for individuals with microcephaly to receive regular monitoring and care from a team of healthcare professionals to address any related medical issues.
Inversions are classified based on their location along the chromosome:
* Interstitial inversion: A segment of DNA is reversed within a larger gene or group of genes.
* Pericentric inversion: A segment of DNA is reversed near the centromere, the region of the chromosome where the sister chromatids are most closely attached.
Chromosome inversions can be detected through cytogenetic analysis, which allows visualization of the chromosomes and their structure. They can also be identified using molecular genetic techniques such as PCR (polymerase chain reaction) or array comparative genomic hybridization (aCGH).
Chromosome inversions are relatively rare in the general population, but they have been associated with various developmental disorders and an increased risk of certain diseases. For example, individuals with an inversion on chromosome 8p have an increased risk of developing cancer, while those with an inversion on chromosome 9q have a higher risk of developing neurological disorders.
Inversions can be inherited from one or both parents, and they can also occur spontaneously as a result of errors during DNA replication or repair. In some cases, inversions may be associated with other genetic abnormalities, such as translocations or deletions.
Overall, chromosome inversions are an important aspect of human genetics and can provide valuable insights into the mechanisms underlying developmental disorders and disease susceptibility.
When a chromosome breaks, it can lead to genetic instability and potentially contribute to the development of diseases such as cancer. Chromosome breakage can also result in the loss or gain of genetic material, which can further disrupt normal cellular function and increase the risk of disease.
There are several types of chromosome breakage, including:
1. Chromosomal aberrations: These occur when there is a change in the number or structure of the chromosomes, such as an extra copy of a chromosome (aneuploidy) or a break in a chromosome.
2. Genomic instability: This refers to the presence of errors in the genetic material that can lead to changes in the function of cells and tissues.
3. Chromosomal fragile sites: These are specific regions of the chromosomes that are more prone to breakage than other regions.
4. Telomere shortening: Telomeres are the protective caps at the ends of the chromosomes, and their shortening can lead to chromosome breakage and genetic instability.
Chromosome breakage can be detected through cytogenetic analysis, which involves staining the cells with dyes to visualize the chromosomes and look for any abnormalities. The detection of chromosome breakage can help diagnose certain diseases, such as cancer, and can also provide information about the risk of disease progression.
In summary, chromosome breakage is a type of genetic alteration that can occur as a result of various factors, including exposure to radiation or chemicals, errors during cell division, or aging. It can lead to genetic instability and increase the risk of diseases such as cancer. Detection of chromosome breakage through cytogenetic analysis can help diagnose certain diseases and provide information about the risk of disease progression.
There are several types of ataxia, each with different symptoms and causes. Some common forms of ataxia include:
1. Spinocerebellar ataxia (SCA): This is the most common form of ataxia and is caused by a degeneration of the cerebellum and spinal cord. It can cause progressive weakness, loss of coordination, and difficulty with speaking and swallowing.
2. Friedreich's ataxia: This is the second most common form of ataxia and is caused by a deficiency of vitamin E in the body. It can cause weakness in the legs, difficulty walking, and problems with speech and language.
3. Ataxia-telangiectasia (AT): This is a rare form of ataxia that is caused by a gene mutation. It can cause progressive weakness, loss of coordination, and an increased risk of developing cancer.
4. Acute cerebellar ataxia: This is a sudden and temporary form of ataxia that can be caused by a variety of factors such as infections, injuries, or certain medications.
5. Drug-induced ataxia: Certain medications can cause ataxia as a side effect.
6. Vitamin deficiency ataxia: Deficiencies in vitamins such as vitamin B12 or folate can cause ataxia.
7. Metabolic disorders: Certain metabolic disorders such as hypothyroidism, hyperthyroidism, and hypoglycemia can cause ataxia.
8. Stroke or brain injury: Ataxia can be a result of a stroke or brain injury.
9. Multiple system atrophy (MSA): This is a rare progressive neurodegenerative disorder that can cause ataxia, parkinsonism, and autonomic dysfunction.
10. Spinocerebellar ataxia (SCA): This is a group of rare genetic disorders that can cause progressive cerebellar ataxia, muscle wasting, and other signs and symptoms.
It's important to note that this is not an exhaustive list and there may be other causes of ataxia not mentioned here. If you suspect you or someone you know may have ataxia, it is important to consult a healthcare professional for proper diagnosis and treatment.
Some examples of multiple abnormalities include:
1. Multiple chronic conditions: An individual may have multiple chronic conditions such as diabetes, hypertension, arthritis, and heart disease, which can affect their quality of life and increase their risk of complications.
2. Congenital anomalies: Some individuals may be born with multiple physical abnormalities or birth defects, such as heart defects, limb abnormalities, or facial deformities.
3. Mental health disorders: Individuals may experience multiple mental health disorders, such as depression, anxiety, and bipolar disorder, which can impact their cognitive functioning and daily life.
4. Neurological conditions: Some individuals may have multiple neurological conditions, such as epilepsy, Parkinson's disease, and stroke, which can affect their cognitive and physical functioning.
5. Genetic disorders: Individuals with genetic disorders, such as Down syndrome or Turner syndrome, may experience a range of physical and developmental abnormalities.
The term "multiple abnormalities" is often used in medical research and clinical practice to describe individuals who have complex health needs and require comprehensive care. It is important for healthcare providers to recognize and address the multiple needs of these individuals to improve their overall health outcomes.
List of OMIM disorder codes
College of Osteopathic Medicine of the Pacific
Artificial transcription factor
1965 in science
Carl H. Johnson
SNRPN upstream reading frame protein
Epigenetics of human development
Multiplex ligation-dependent probe amplification
Fluorescence in situ hybridization
Transgenerational epigenetic inheritance
List of skin conditions
27 Crocus Place
Index of education articles
List of fetal abnormalities
Phospholipid-transporting ATPase VA
Epigenetics in stem-cell differentiation
Giovanni Francesco Caroto
Causes of seizures
Small supernumerary marker chromosome
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- Buiting K. Prader-Willi syndrome and Angelman syndrome. (nih.gov)
- He said that my son has Angelman Syndrome, or Prader-Willi Syndrome. (nolafamily.com)
- Deletion of chromosome region 15q12 causes both Angelman Syndrome and a totally different disorder called Prader-Willi Syndrome. (cnsfoundation.org)
- While the deleted chromosome is of maternal origin in Angelman Syndrome, it is the paternal chromosome that is partially deleted in the Prader-Willi Syndrome. (cnsfoundation.org)
Cure for Angelman1
- This is part of FAST's Pillar 2 approach in the Roadmap to a Cure for Angelman syndrome. (cureangelman.org)
- Angelman syndrome is a genetic disorder that primarily affects the nervous system. (nih.gov)
- Most cases of Angelman syndrome are not inherited, although in rare cases a genetic change responsible for Angelman syndrome can be inherited from a parent. (nih.gov)
- His suggestion was to visit a neurologist and a geneticist, believing Jayden to either have Fragile X Syndrome, a genetic condition helmed by intellectual and cognitive impairment, or Angelman Syndrome, an answer to why Jayden was developmentally delayed. (nolafamily.com)
- Angelman Syndrome is a genetic disorder that causes developmental delay and neurological problems. (cnsfoundation.org)
- She has particular expertise in rare genetic developmental disorders in children, including Angelman syndrome, Pitt-Hopkins syndrome, SLC6A1-related disorders, Phelan-McDermid Syndrome, and Rett syndrome. (utsouthwestern.edu)
- New AI-based technologies are changing how genetic syndromes and rare diseases are diagnosed. (prweb.com)
- This is especially true for genetic syndromes where the precise cause, or genetic mutation, is often unknown. (prweb.com)
- Intellectual development delay, and disability, can also be a symptom or feature of some genetic syndromes. (prweb.com)
- In some cases, with hypermobile Ehlers-Danlos (EDS) where there is no current known genetic cause identified, and so no genetic testing available, genetic experts rely on an individual's symptoms to diagnose this form of the syndrome. (prweb.com)
- When Do Symptoms of Angelman syndrome Begin? (nih.gov)
- However, loss of the OCA2 gene does not cause the other signs and symptoms of Angelman syndrome. (nih.gov)
- The loss of tonic inhibition has been proposed to be a fundamental mechanism underlying many of the symptoms of Angelman Syndrome. (cureangelman.es)
- The syndrome is named for physicians Walter Dandy and Arthur Walker who described associated signs and symptoms of the syndrome in the 1900s. (asu.edu)
- The Alagille Syndrome market report gives a thorough understanding of the Alagille Syndrome by including details such as disease definition, symptoms, causes, pathophysiology, diagnosis and treatment. (researchandmarkets.com)
- They are particularly focused on developing transformative treatments for Dup15q syndrome, Pitt-Hopkins syndrome, and Angelman syndrome. (nih.gov)
- Moreover, it suggests that cases of clinically suspected Angelman syndrome without molecular confirmation should undergo exome or genome sequencing, as novel neurodevelopmental syndromes with phenotypes overlapping with Angelman continue to be discovered. (bvsalud.org)
- In a small percentage of cases, Angelman syndrome results when a person inherits two copies of chromosome 15 from his or her father (paternal copies) instead of one copy from each parent. (nih.gov)
- Metabolic Syndromes, Omics Technologies for Clinical Diagnosis and Gene Therapy: Medical Applications in Human Genetics (2022) 1: 242. (benthamscience.com)
- Many of the characteristic features of Angelman syndrome result from the loss of function of a gene called UBE3A. (nih.gov)
- In other cases (about 10 to 20 percent), Angelman syndrome is caused by a variant in the maternal copy of the UBE3A gene. (nih.gov)
- Rarely, Angelman syndrome can also be caused by a chromosomal rearrangement called a translocation, or by a variant or other defect in the region of DNA that controls activation of the UBE3A gene. (nih.gov)
- An exciting publication in Science Translational Medicine titled "An ASO therapy for Angelman syndrome that targets an evolutionarily conserved region at the start of the UBE3A-AS transcript" has just been released discussing the extensive research behind one of the first investigational molecular therapies intended for Angelman syndrome that is currently in clinical trials (ClinicalTrials.gov, NCT04259281). (cureangelman.org)
- This means there is very little or no UBE3A protein being made in the brain of individuals living with Angelman syndrome. (cureangelman.org)
- In Angelman syndrome, loss of the UBE3A gene function leads to a build up of proteins that are normally marked by the cell machinery ("tagged") for degradation and recycling by the Ube3a system. (cureangelman.es)
- A ketogenic diet safely and rapidly controlled treatment-resistant prolonged non-convulsive seizure activity in two girls with Angelman syndrome caused by a new mutation in the UBE3A gene, a study shows. (cureepilepsy.org)
- Epilepsy and seizures are also common with this disorder, and Jayden's experience was no exception, having suffered seizures since he was 15 months old, in addition to being diagnosed with Lennox Gastaut Syndrome, a type of epilepsy. (nolafamily.com)
- Physical examination helps in the diagnosis of specific epileptic syndromes that cause abnormal findings, such as dermatologic abnormalities (eg, patients with intractable generalized tonic-clonic seizures for years are likely to have injuries requiring stitches). (medscape.com)
- These cases highlight the ketogenic diet as an effective approach to manage prolonged non-convulsive seizures related to Angelman and suggest that carbohydrate restriction may, by itself, have an effect on these seizures. (cureepilepsy.org)
- Metabolic Syndromes (MetS) are recognized as a cluster of risk factors which are known to increase the likelihood of obesity, type 2 diabetes (T2D) and cardiovascular disorders (CVDs). (benthamscience.com)
- A syndrome characterized by multiple abnormalities, MENTAL RETARDATION , and movement disorders. (nih.gov)
- With additional testing, it was confirmed that Jayden had Angelman Syndrome (AS), a neurogenetic disorder that affects the nervous system causing significant developmental delay, speech impairment, and troubles with balance. (nolafamily.com)
- Recurrent de novo missense variants in H4 histone genes have recently been associated with a novel neurodevelopmental syndrome that is characterized by intellectual disability and developmental delay as well as more variable findings that include short stature, microcephaly , and facial dysmorphisms. (bvsalud.org)
- In some cases, this developmental delay extends into adulthood and becomes known as a developmental disability, for example, most children diagnosed with Angelman syndrome never learn to talk, or use more than a few words to communicate. (prweb.com)
- The causes of Angelman syndrome are unknown in 10 to 15 percent of affected individuals. (nih.gov)
- The mission of the Angelman Syndrome Foundation is to advance the awareness and treatment of Angelman syndrome through education and information, research, and support for individuals with Angelman syndrome, their families and other concerned parties. (angelman.org)
- A comparison of our proband's findings to the initial description of the H4-associated neurodevelopmental syndrome demonstrates that his phenotype closely matches the spectrum of those reported among the 29 affected individuals. (bvsalud.org)
- The Alagille Syndrome market report provides current treatment practices, emerging drugs, Alagille Syndrome market share of the individual therapies, current and forecasted Alagille Syndrome market Size from 2019 to 2032 segmented by seven major markets. (researchandmarkets.com)
- It covers the details of conventional and current medical therapies available in the Alagille Syndrome market for the treatment of the condition. (researchandmarkets.com)
- The report provides the details of the emerging therapies under the late and mid-stage of development for Alagille Syndrome treatment. (researchandmarkets.com)
- The Alagille Syndrome market outlook of the report helps to build the detailed comprehension of the historic, current, and forecasted Alagille Syndrome market trends by analyzing the impact of current therapies on the market, unmet needs, drivers and barriers and demand of better technology. (researchandmarkets.com)
- This section provides the total Alagille Syndrome market size and market size by therapies in the United States. (researchandmarkets.com)
- Quinn, E . & Rowland, C. (2017) Exploring expressive communication skills in a cross-sectional sample of children and young adults with Angelman syndrome. (ohsu.edu)
- 2021. Perineuronal net degradation rescues CA2 plasticity in a mouse model of Rett syndrome. (nih.gov)
- In this new paper, Dr. Scott Dindot and his team shared how they sought to optimize an investigational ASO candidate for Angelman syndrome. (cureangelman.org)
- This technique is also used to characterize the type of seizure and epileptic syndrome to optimize pharmacologic treatment and for presurgical workup. (medscape.com)
- Ovid Therapeutics: Ovid therapeutics is currently assessing the development of OV-101 for the treatment of Angelman Syndrome. (cureangelman.es)
- The Report also covers current Alagille Syndrome treatment practice/algorithm, market drivers, market barriers and unmet medical needs to curate best of the opportunities and assesses the underlying potential of the market. (researchandmarkets.com)
- It also provides Alagille Syndrome treatment algorithms and guidelines in the United States, Europe, and Japan. (researchandmarkets.com)
- The report provides the details of the marketed product available for Alagille Syndrome treatment. (researchandmarkets.com)
- These include Rets syndrome, Angelman syndrome, MeCP2 duplication, and spinal muscular atrophy and giant axonal neuropathy. (nih.gov)
- It also helps to understand the Alagille Syndrome clinical trial details, expressive pharmacological action, agreements and collaborations, approval and patent details, advantages and disadvantages of each included drug and the latest news and press releases. (researchandmarkets.com)
- Video-EEG monitoring is the standard test for classifying the type of seizure or syndrome or to diagnose pseudoseizures (ie, to establish a definitive diagnosis of spells with impairment of consciousness). (medscape.com)
- Selection of an anticonvulsant medication depends on an accurate diagnosis of the epileptic syndrome. (medscape.com)
- Drug chapter segment of the Alagille Syndrome report encloses the detailed analysis of Alagille Syndrome marketed drugs and late stage (Phase-III and Phase-II) pipeline drugs. (researchandmarkets.com)
- Novel experimental approaches and pharmacological treatments can provide a better insight into metabolic syndrome and its related complications, thereby reducing its global burden. (benthamscience.com)
- H4C5 missense variant leads to a neurodevelopmental phenotype overlapping with Angelman syndrome. (bvsalud.org)
- To combat the effects of Angelman Syndrome, Jayden has been in therapy since he was 10 months old. (nolafamily.com)
- The epidemiology segment also provides the Alagille Syndrome epidemiology data and findings across the United States, EU5 (Germany, France, Italy, Spain, and the United Kingdom), and Japan. (researchandmarkets.com)
- 8. Loss of Angelman Syndrome Protein E6AP Disrupts a Novel Antagonistic Estrogen-Retinoic Acid Transcriptional Crosstalk in Neurons. (nih.gov)
- This segment of the report covers the detailed diagnostic methods or tests for Alagille Syndrome. (researchandmarkets.com)
- The ultimate clinical result, as extrapolated from tests in the mouse models of Angelman syndrome, is hoped to be improvements in various aspects of the syndrome including motor function, sleep and behavior. (cureangelman.es)
- Dandy-Walker Syndrome is a congenital brain defect in humans characterized by malformations to the cerebellum, the part of the brain that controls movement, and to the ventricles, the fluid-filled cavities that surround the cerebellum. (asu.edu)
- Fetal Alcohol Syndrome (FAS) is the sum total of the damage done to the child before birth as a result of the mother drinking alcohol during pregnancy. (cnsfoundation.org)
- This "Alagille Syndrome- Market Insights, Epidemiology, and Market Forecast-2032" report delivers an in-depth understanding of the Alagille Syndrome, historical and forecasted epidemiology as well as the Alagille Syndrome market trends in the United States, EU5 (Germany, Spain, Italy, France, and United Kingdom) and Japan. (researchandmarkets.com)
- The disease epidemiology covered in the report provides historical as well as forecasted Alagille Syndrome epidemiology scenario in the 7MM covering the United States, EU5 countries (Germany, Spain, Italy, France, and the United Kingdom), and Japan from 2019 to 2032. (researchandmarkets.com)
- The Alagille Syndrome epidemiology division provide insights about historical and current Alagille Syndrome patient pool and forecasted trend for every seven major countries. (researchandmarkets.com)