Pelizaeus-Merzbacher Disease
Myelin Proteolipid Protein
Diffuse Cerebral Sclerosis of Schilder
Spastic Paraplegia, Hereditary
Myelin Proteins
MR-revealed myelination in the cerebral corticospinal tract as a marker for Pelizaeus-Merzbacher's disease with proteolipid protein gene duplication. (1/59)
BACKGROUND AND PURPOSE: Pelizaeus-Merzbacher's disease (PMD) is caused by mutations in the proteolipid protein (PLP) gene. Recent studies have shown that an increased PLP dosage, resulting from total duplication of the PLP gene, invariably causes the classic form of PMD. The purpose of this study was to compare the MR findings of PMD attributable to PLP duplication with those of PMD arising from a missense mutation. METHODS: Seven patients with PMD, three with a PLP missense mutation in either exon 2 or 5 (patients 1-3), and four with PLP duplication (patient 4 having larger PLP duplication than patients 5-7) were clinically classified as having either the classic or connatal form of PMD. Cerebral MR images were obtained to analyze the presence of myelination and T1 and T2 shortening in the deep gray matter. Multiple MR studies were performed in six of the seven patients to analyze longitudinal changes. RESULTS: Four patients (patients 1-4) were classified as having connatal PMD, whereas the other three (patients 5-7) were classified as having classic PMD. Myelination in the cerebral corticospinal tract, optic radiation, and corpus callosum was observed in three cases of classic PMD with PLP duplication. In patient 4, myelination extended to the internal capsule, corona radiata, and centrum semiovale over a 3-year period. No myelination was observed in three PMD cases with a PLP point mutation. T2 shortening in the deep gray matter was recognized in all patients with PMD. CONCLUSION: The presence of myelination in the cerebral corticospinal tract with diffuse white matter hypomyelination on MR images could be a marker for PMD with PLP duplication. It is suggested that progression of myelination may be present in connatal PMD with large PLP duplication. (+info)Additional copies of the proteolipid protein gene causing Pelizaeus-Merzbacher disease arise by separate integration into the X chromosome. (2/59)
The proteolipid protein gene (PLP) is normally present at chromosome Xq22. Mutations and duplications of this gene are associated with Pelizaeus-Merzbacher disease (PMD). Here we describe two new families in which males affected with PMD were found to have a copy of PLP on the short arm of the X chromosome, in addition to a normal copy on Xq22. In the first family, the extra copy was first detected by the presence of heterozygosity of the AhaII dimorphism within the PLP gene. The results of FISH analysis showed an additional copy of PLP in Xp22.1, although no chromosomal rearrangements could be detected by standard karyotype analysis. Another three affected males from the family had similar findings. In a second unrelated family with signs of PMD, cytogenetic analysis showed a pericentric inversion of the X chromosome. In the inv(X) carried by several affected family members, FISH showed PLP signals at Xp11.4 and Xq22. A third family has previously been reported, in which affected members had an extra copy of the PLP gene detected at Xq26 in a chromosome with an otherwise normal banding pattern. The identification of three separate families in which PLP is duplicated at a noncontiguous site suggests that such duplications could be a relatively common but previously undetected cause of genetic disorders. (+info)Concepts of myelin and myelination in neuroradiology. (3/59)
Until the advent of MR imaging, knowledge of the structure of myelin and the process of myelination were of little importance to the neuroradiologist. Other than some mild changes in the attenuation of white matter, myelination resulted in no significant alterations of CT (1) or sonographic studies. MR studies, on the other hand, have been increasingly used for pediatric brain imaging. MR imaging's greater sensitivity to small changes in the water content of brain tissue, to changes in the binding of free water (revealed by magnetization transfer), and to the extent and anisotropy of water diffusion (revealed by diffusion imaging) has cast new light on this very complex and important molecule. Assessing myelination has become a key component of evaluating the child with delayed development. Moreover, better understanding of the nature of myelin and the effect of its different components on MR imaging parameters may help us to understand and diagnose inborn errors of metabolism better. In this review, I discuss what is known regarding the function and structure of CNS myelin and the effects of the various components of myelin on the signal imparted to the MR image. Summary Abnormalities of myelin can cause a wide variety of disorders of the nervous system. MR imaging is a powerful tool for the study of myelin and its disorders. However, only by understanding the physiologic properties and structure of myelin can we use MR imaging to its fullest capacity for studying patients with myelin disorders. In this review, I have discussed the structure of myelin as it relates to MR imaging of normal myelination and to neurologic disorders resulting from abnormalities of myelin. Thinking of myelin and its disorders in this manner will be critical to using MR imaging techniques optimally to diagnose and study these disorders further. (+info)X inactivation phenotype in carriers of Pelizaeus-Merzbacher disease: skewed in carriers of a duplication and random in carriers of point mutations. (4/59)
Pelizaeus-Merzbacher disease (PMD) is an X-linked recessive disease caused by coding sequence mutations in the PLP gene, sub-microscopic duplications of variable sizes including the PLP gene or very rarely deletions of the PLP gene. We analysed the X inactivation pattern in blood of PMD female carriers with duplications and with point mutations. In the majority of duplication carriers (7/11), the X chromosome bearing the duplication was preferentially inactivated, whereas a random pattern of X inactivation was detected in point mutation carriers (3/3), a deletion carrier (1/1), affected females (4/4) who did not have a recognised mutation and normal control females. However 2/5 non-carrier female relatives of patients with a duplication, had skewed X inactivation. The skewed pattern of inactivation observed in most duplication carriers and not in mutation carriers suggests a) that there is selection against those cells in which the duplicated X chromosome is active and b) other expressed sequences within the duplicated region rather than mutant PLP may be responsible. Since the skewed X inactivation did not segregate with the disease in two families and the pattern of X inactivation was variable among the duplication carriers, the pattern X inactivation is an unsuitable diagnostic tool for female carriers of PMD. (+info)Genotype-phenotype correlation in inherited brain myelination defects due to proteolipid protein gene mutations. Clinical European Network on Brain Dysmyelinating Disease. (5/59)
Pelizaeus-Merzbacher disease (PMD) and spastic paraplegia type 2 (SPG2) are X-linked developmental defects of myelin formation affecting the central nervous system (CNS). They differ clinically in the onset and severity of the motor disability but both are allelic to the proteolipid protein gene (PLP), which encodes the principal protein components of CNS myelin, PLP and its spliced isoform, DM20. We investigated 52 PMD and 28 SPG families without large PLP duplications or deletions by genomic PCR amplification and sequencing of the PLP gene. We identified 29 and 4 abnormalities respectively. Patients with PLP mutations presented a large range of disease severity, with a continuum between severe forms of PMD, without motor development, to pure forms of SPG. Clinical severity was found to be correlated with the nature of the mutation, suggesting a distinct strategy for detection of PLP point mutations between severe PMD, mild PMD and SPG. Single amino-acid changes in highly conserved regions of the DM20 protein caused the most severe forms of PMD. Substitutions of less conserved amino acids, truncations, absence of the protein and PLP-specific mutations caused the milder forms of PMD and SPG. Therefore, the interactions and stability of the mutated proteins has a major effect on the severity of PLP-related diseases. (+info)Patients lacking the major CNS myelin protein, proteolipid protein 1, develop length-dependent axonal degeneration in the absence of demyelination and inflammation. (6/59)
Axonal degeneration contributes to clinical disability in the acquired demyelinating disease multiple sclerosis. Axonal degeneration occurs during acute attacks, associated with inflammation, and during the chronic progressive phase of the disease in which inflammation is not prominent. To explore the importance of interactions between oligodendrocytes and axons in the CNS, we analysed the brains of rodents and humans with a null mutation in the gene encoding the major CNS myelin protein, proteolipid protein (PLP1, previously PLP). Histological analyses of the CNS of Plp1 null mice and of autopsy material from patients with null PLP1 mutations were performed to evaluate axonal and myelin integrity. In vivo proton magnetic resonance spectroscopy (MRS) of PLP1 null patients was conducted to measure levels of N-acetyl aspartate (NAA), a marker of axonal integrity. Length-dependent axonal degeneration without demyelination was identified in the CNS of Plp1 null mice. Proton MRS of PLP1-deficient patients showed reduced NAA levels, consistent with axonal loss. Analysis of patients' brain tissue also demonstrated a length-dependent pattern of axonal loss without significant demyelination. Therefore, axonal degeneration occurs in humans as well as mice lacking the major myelin protein PLP1. This degeneration is length-dependent, similar to that found in the PNS of patients with the inherited demyelinating neuropathy, CMT1A, but is not associated with significant demyelination. Disruption of PLP1-mediated axonal--glial interactions thus probably causes this axonal degeneration. A similar mechanism may be responsible for axonal degeneration and clinical disability that occur in patients with multiple sclerosis. (+info)Overexpression of the myelin proteolipid protein leads to accumulation of cholesterol and proteolipid protein in endosomes/lysosomes: implications for Pelizaeus-Merzbacher disease. (7/59)
Duplications and overexpression of the proteolipid protein (PLP) gene are known to cause the dysmyelinating disorder Pelizaeus-Merzbacher disease (PMD). To understand the cellular response to overexpressed PLP in PMD, we have overexpressed PLP in BHK cells and primary cultures of oligodendrocytes with the Semliki Forest virus expression system. Overexpressed PLP was routed to late endosomes/lysosomes and caused a sequestration of cholesterol in these compartments. Similar results were seen in transgenic mice overexpressing PLP. With time, the endosomal/lysosomal accumulation of cholesterol and PLP led to an increase in the amount of detergent-insoluble cellular cholesterol and PLP. In addition, two fluorescent sphingolipids, BODIPY-lactosylceramide and -galactosylceramide, which under normal conditions are sorted to the Golgi apparatus, were missorted to perinuclear structures. This was also the case for the lipid raft marker glucosylphosphatidylinositol-yellow fluorescence protein, which under normal steady-state conditions is localized on the plasma membrane and to the Golgi complex. Taken together, we show that overexpression of PLP leads to the formation of endosomal/lysosomal accumulations of cholesterol and PLP, accompanied by the mistrafficking of raft components. We propose that these accumulations perturb the process of myelination and impair the viability of oligodendrocytes. (+info)Genomic rearrangements resulting in PLP1 deletion occur by nonhomologous end joining and cause different dysmyelinating phenotypes in males and females. (8/59)
In the majority of patients with Pelizaeus-Merzbacher disease, duplication of the proteolipid protein gene PLP1 is responsible, whereas deletion of PLP1 is infrequent. Genomic mechanisms for these submicroscopic chromosomal rearrangements remain unknown. We identified three families with PLP1 deletions (including one family described elsewhere) that arose by three distinct processes. In one family, PLP1 deletion resulted from a maternal balanced submicroscopic insertional translocation of the entire PLP1 gene to the telomere of chromosome 19. PLP1 on the 19qtel is probably inactive by virtue of a position effect, because a healthy male sibling carries the same der(19) chromosome along with a normal X chromosome. Genomic mapping of the deleted segments revealed that the deletions are smaller than most of the PLP1 duplications and involve only two other genes. We hypothesize that the deletion is infrequent, because only the smaller deletions can avoid causing either infertility or lethality. Analyses of the DNA sequence flanking the deletion breakpoints revealed Alu-Alu recombination in the family with translocation. In the other two families, no homologous sequence flanking the breakpoints was found, but the distal breakpoints were embedded in novel low-copy repeats, suggesting the potential involvement of genome architecture in stimulating these rearrangements. In one family, junction sequences revealed a complex recombination event. Our data suggest that PLP1 deletions are likely caused by nonhomologous end joining. (+info)Pelizaeus-Merzbacher disease (PMD) is a rare X-linked recessive genetic disorder affecting the nervous system. It is caused by mutations in the PLP1 gene, which provides instructions for making proteins that are important for the formation and maintenance of the myelin sheath, the protective covering that wraps around nerve cell fibers (axons) in the brain and spinal cord to ensure efficient transmission of electrical signals.
In individuals with PMD, the myelin sheath is either partially or completely absent, leading to progressive neurological symptoms. The classic form of PMD is characterized by early onset of nystagmus (involuntary eye movements), ataxia (loss of muscle coordination and balance), and intellectual disability. Other features may include hypotonia (low muscle tone), spasticity (stiff or rigid muscles), and seizures. The severity and progression of the disease can vary widely among affected individuals, ranging from a severe, lethal form to a milder form with a slower disease course.
Currently, there is no cure for PMD, and treatment is focused on managing symptoms and improving quality of life.
Myelin Proteolipid Protein (PLP) is a major component of the myelin sheath, which is a fatty insulating substance that covers and protects nerve fibers in the central nervous system (CNS). PLP makes up about 50% of the proteins found in the myelin sheath. It plays a crucial role in the structure and function of the myelin sheath, including maintaining its compactness and stability. Defects or mutations in the gene that encodes for PLP can lead to various demyelinating diseases, such as X-linked adrenoleukodystrophy (X-ALD) and Pelizaeus-Merzbacher disease (PMD), which are characterized by the degeneration of the myelin sheath and subsequent neurological impairments.
Diffuse cerebral sclerosis of Schilder, also known as Schilder's disease, is a rare inflammatory demyelinating disorder of the central nervous system. It primarily affects children and young adults, but can occur at any age. The condition is characterized by widespread destruction of the myelin sheath, which surrounds and protects nerve fibers in the brain.
The hallmark feature of Schilder's disease is the presence of multiple, large, symmetrical lesions in the white matter of both cerebral hemispheres. These lesions are typically located in the parieto-occipital regions of the brain and can extend to involve other areas as well.
The symptoms of Schilder's disease vary depending on the location and extent of the lesions, but may include:
* Progressive intellectual decline
* Seizures
* Visual disturbances
* Weakness or paralysis on one side of the body (hemiparesis)
* Loss of sensation in various parts of the body
* Speech difficulties
* Behavioral changes, such as irritability, mood swings, and depression
The exact cause of Schilder's disease is not known, but it is believed to be an autoimmune disorder, in which the body's own immune system mistakenly attacks the myelin sheath. There is no cure for Schilder's disease, and treatment typically involves corticosteroids or other immunosuppressive therapies to reduce inflammation and slow the progression of the disease. Despite treatment, many patients with Schilder's disease experience significant disability and may require long-term care.
Hereditary Spastic Paraplegia (HSP) is a group of genetic disorders that affect the long motor neurons in the spinal cord, leading to lower limb spasticity and weakness. It is characterized by progressive stiffness and contraction of the leg muscles, resulting in difficulty with walking and balance.
The symptoms of HSP typically begin in childhood or early adulthood and worsen over time. The severity of the condition can vary widely, even within the same family, depending on the specific genetic mutation involved. In addition to lower limb spasticity, some individuals with HSP may also experience bladder dysfunction, sensory loss, or other neurological symptoms.
HSP is inherited in an autosomal dominant or autosomal recessive pattern, depending on the specific genetic mutation involved. There are over 70 different genes that have been identified as causing HSP, and genetic testing can be used to confirm the diagnosis and identify the specific genetic mutation responsible.
Treatment for HSP is focused on managing symptoms and maintaining mobility. Physical therapy, orthotics, and medications such as baclofen or tizanidine may be used to help reduce muscle spasticity and improve mobility. In some cases, surgery may be necessary to relieve muscle contractures or other complications.
I'm sorry for any confusion, but "Jimpy" is not a recognized medical term or condition associated with mice in the field of veterinary medicine. It may be a colloquial or informal term used to describe a particular characteristic or behavior in mice, but without further context, it's challenging to provide an accurate definition. If you could provide more information about where you encountered this term or its intended meaning, I would be happy to help you further.
Myelin proteins are proteins that are found in the myelin sheath, which is a fatty (lipid-rich) substance that surrounds and insulates nerve fibers (axons) in the nervous system. The myelin sheath enables the rapid transmission of electrical signals (nerve impulses) along the axons, allowing for efficient communication between different parts of the nervous system.
There are several types of myelin proteins, including:
1. Proteolipid protein (PLP): This is the most abundant protein in the myelin sheath and plays a crucial role in maintaining the structure and function of the myelin sheath.
2. Myelin basic protein (MBP): This protein is also found in the myelin sheath and helps to stabilize the compact structure of the myelin sheath.
3. Myelin-associated glycoprotein (MAG): This protein is involved in the adhesion of the myelin sheath to the axon and helps to maintain the integrity of the myelin sheath.
4. 2'3'-cyclic nucleotide 3' phosphodiesterase (CNP): This protein is found in oligodendrocytes, which are the cells that produce the myelin sheath in the central nervous system. CNP plays a role in maintaining the structure and function of the oligodendrocytes.
Damage to myelin proteins can lead to demyelination, which is a characteristic feature of several neurological disorders, including multiple sclerosis (MS), Guillain-Barré syndrome, and Charcot-Marie-Tooth disease.
The X chromosome is one of the two types of sex-determining chromosomes in humans (the other being the Y chromosome). It's one of the 23 pairs of chromosomes that make up a person's genetic material. Females typically have two copies of the X chromosome (XX), while males usually have one X and one Y chromosome (XY).
The X chromosome contains hundreds of genes that are responsible for the production of various proteins, many of which are essential for normal bodily functions. Some of the critical roles of the X chromosome include:
1. Sex Determination: The presence or absence of the Y chromosome determines whether an individual is male or female. If there is no Y chromosome, the individual will typically develop as a female.
2. Genetic Disorders: Since females have two copies of the X chromosome, they are less likely to be affected by X-linked genetic disorders than males. Males, having only one X chromosome, will express any recessive X-linked traits they inherit.
3. Dosage Compensation: To compensate for the difference in gene dosage between males and females, a process called X-inactivation occurs during female embryonic development. One of the two X chromosomes is randomly inactivated in each cell, resulting in a single functional copy per cell.
The X chromosome plays a crucial role in human genetics and development, contributing to various traits and characteristics, including sex determination and dosage compensation.
Pelizaeus-Merzbacher disease
Proteolipid protein 1
Paul J. Tesar
Antisense therapy
Tubulin beta-4A chain
Monocarboxylate transporter 8
Ohad Birk
Myelinoid
Autosomal dominant leukodystrophy with autonomic disease
GJC2
Ultra-conserved element
Myelin
Myelin proteolipid protein
Connexin
Gene duplication
Ludwig Merzbacher
Gap junction
The Myelin Project
Gretchen Mol
The Stennis Foundation
David Rowitch
Friedrich Christoph Pelizaeus
Chorea gravidarum
List of MeSH codes (C16)
Nystagmus
List of diseases (P)
PLP
PMD
List of MeSH codes (C10)
List of neurological conditions and disorders
Pelizaeus-Merzbacher disease - Wikipedia
Pelizaeus-Merzbacher Disease: Background, Etiology, Epidemiology
Pelizaeus Merzbacher Disease Support Group - National Organization for Rare Disorders
Pelizaeus-Merzbacher Disease: Background, Etiology, Epidemiology
Neural stem cells restore myelin in a demyelinating model of Pelizaeus-Merzbacher disease - Enlighten Publications
Pelizaeus-Merzbacher Disease | Profiles RNS
Pelizaeus-Merzbacher Disease: Background, Etiology, Epidemiology
Pelizaeus-Merzbacher Disease Treatment & Management: Approach Considerations, Consultations
Center for Pediatric Research - Molecular Mechanisms of Pelizaeus-Merzbacher Disease
"Pelizaeus-Merzbacher disease"[Clinical Features] OR 61440[uid] - MedGen -...
Novel mutations in the GJC2 gene associated with Pelizaeus-Merzbacher-like disease.
Proteinopathy - Wikipedia
MedlinePlus: Genetic Conditions: P
PLP1 proteolipid protein 1 [Homo sapiens (human)] - Gene - NCBI
Hereditary spastic paraplegia 2 AND humans[mesh] AND review[publication type] - Search Results - PubMed
Oligodendrocyte Death in Pelizaeus-Merzbacher Disease Is Rescued by Iron Chelation - Fingerprint - Rutgers, The State...
Pelizaeus-Merzbacher Disease Market is Expected to Expand at a Healthy Growth Rate During the Study Period (2019-2032)| Key...
Pelizaeus-Merzbacher Disease Market is Expected to Expand at a Healthy Growth Rate During the Study Period (2019-2032)| Key...
Wall of Fame
Accurate detection of complex structural variations using single-molecule sequencing | Nature Methods
neuropathology blog: March 2008
A new X linked neurodegenerative syndrome with mental retardation, blindness, convulsions, spasticity, mild hypomyelination,...
PEDIATRIC NEURORADIOLOGY | American Journal of Neuroradiology
PDF) No Meaningful Apology for American Indian Unethical Research Abuses
Clinical trials for stem cell therapies | BMC Medicine | Full Text
Andrew Zimmerman | Profiles RNS
Racine & Me April 22, 2018: Keshaun Brown, gET bEHIND the aRTS 2018, the Search for Agent 22, and the Racine Zoo
Accurate detection of complex structural variations using single-molecule sequencing, Nature Methods | 10.1038/s41592-018-0001...
Survival of, and competition between, oligodendrocytes expressing different alleles of the Plp gene | Journal of Cell Biology ...
Geometry.Net - Health Conditions: Krabbe Disease
Form of Pelizaeus-Merzbac2
- Deletions of PLP1 locus (which are rare) cause a milder form of Pelizaeus-Merzbacher disease than is observed with the typical duplication mutations, which demonstrates the critical importance of gene dosage at this locus for normal CNS function. (wikipedia.org)
- Neonates with the connatal form of Pelizaeus-Merzbacher disease should be evaluated by a pulmonologist and perhaps by a neonatal swallowing specialist to evaluate airway safety and swallowing safety, respectively. (medscape.com)
Forms of Pelizaeus-Merzbac2
- The several forms of Pelizaeus-Merzbacher disease include classic, congenital, transitional, and adult variants. (wikipedia.org)
- Severe clinical syndromes (sometimes referred to as the connatal forms of Pelizaeus-Merzbacher disease) are typically caused by missense and other small mutations that affect critical positions in PLP1 , whereas the milder spastic paraplegia syndrome is caused by mutations that presumably affect less critical regions of the protein. (medscape.com)
Classic Pelizaeus-Merzbac1
- Most individuals with PLP1 duplications present with classic Pelizaeus-Merzbacher disease, typified by nystagmus that begins in the first year of life, delayed motor and cognitive milestones, and ataxia. (medscape.com)
Vanishing White Matter Disease1
- These diseases, which include Tay-Sachs, Krabbe's, Canavan's, Pelizaeus-Merzbacher, Vanishing White Matter Disease and a host of others are each rare, but collectively they kill thousands of children every year. (news-medical.net)
PLP115
- Pelizaeus-Merzbacher disease is caused by X-linked recessive mutations in the major myelin protein proteolipid protein 1 (PLP1). (wikipedia.org)
- Although Pelizaeus-Merzbacher disease and X-linked spastic paraplegia type 2 are nosologically distinguished, they are at opposite ends of a clinical spectrum of X-linked diseases caused by mutations of the same gene, the proteolipid protein 1 ( PLP1 ) gene, and result in defective central nervous system (CNS) myelination (see the image below). (medscape.com)
- The most common mutations that cause Pelizaeus-Merzbacher disease are duplications of a region of the X chromosome that includes the entire PLP1 gene. (medscape.com)
- In most cases, Pelizaeus-Merzbacher disease is caused by mutations of PLP1 on the long arm of the X chromosome (Xq22). (medscape.com)
- Approximately 60-70% of cases of Pelizaeus-Merzbacher disease result from duplications of the region of the X chromosome that contains PLP1 (caused, it has been proposed, by defective deoxyribonucleic acid [DNA] replication). (medscape.com)
- Some patients with Pelizaeus-Merzbacher disease have been found to have 3 or more copies of the PLP1 gene. (medscape.com)
- Pelizaeus-Merzbacher disease is a fatal X-linked leukodystrophy caused by mutations in the PLP1 gene, which is expressed in the CNS by oligodendrocytes. (gla.ac.uk)
- In the absence of an effective treatment, direct cell transplantation into the CNS to restore myelin has been tested in animal models of severe forms of the disease with failure of developmental myelination, and more recently, in severely affected patients with early disease onset due to point mutations in the PLP1 gene, and absence of myelin by MRI. (gla.ac.uk)
- In patients with a PLP1 duplication mutation, the most common cause of Pelizaeus-Merzbacher disease, the pathology is poorly defined because of a paucity of autopsy material. (gla.ac.uk)
- To address this, we examined two elderly patients with duplication of PLP1 in whom the overall syndrome, including end-stage pathology, indicated a complex disease involving dysmyelination, demyelination and axonal degeneration. (gla.ac.uk)
- Pelizaeus-Merzbacher disease (PMD) is an X-linked leukodystrophy caused by genetic defects of the proteolipid protein 1 gene (PLP1) that encodes the major central nervous system myelin protein. (centerforpediatricresearch.org)
- Hobson, G., Stabley, D., Funanage, V., and Marks, H. A new polymorphism in the proteolipid protein (PLP1) gene and its use for carrier detection of PLP1 gene duplication in Pelizaeus-Merzbacher disease. (centerforpediatricresearch.org)
- PLP1 disorders of central nervous system myelin formation include a range of phenotypes from Pelizaeus-Merzbacher disease (PMD) to spastic paraplegia 2 (SPG2). (nih.gov)
- Novel Insight into the Potential Pathogenicity of Mitochondrial Dysfunction Resulting from PLP1 Duplication Mutations in Patients with Pelizaeus-Merzbacher Disease. (nih.gov)
- Mutations in the PLP1 gene cause Pelizaeus-Merzbacher disease. (southdakotachronicle.com)
Mutations4
- Approximately 15-20% of mutations in Pelizaeus-Merzbacher disease are point mutations or other small mutations that result in base substitutions, insertions, or deletions. (medscape.com)
- Novel mutations in the GJC2 gene associated with Pelizaeus-Merzbacher-like disease. (cegat.com)
- Mutations in this gene cause Pelizaeus-Merzbacher disease and spastic paraplegia type 2. (nih.gov)
- If the dish is too crowded, rad3 is similar at the sequence level to ATM, mutations in which lead to poxitions of the disease ataxia telangiectasia in humans. (top5binarybrokers.com)
Gene4
- The disease is caused by a mutation in the gene that controls the production of a myelin protein. (cam.ac.uk)
- However, other mechanisms of disease causation have also been described where (1) a breakpoint disrupts or alters gene expression via a position effect 7 or (2) a cryptic deletion or duplication is identified at the translocation breakpoint. (bmj.com)
- Identification of Inflammatory, Metabolic, and Cell Survival Pathways Contributing to Cerebral Small Vessel Disease by Postmortem Gene Expression Microarray. (unibas.ch)
- A knowledge graph of biological entities such as genes, gene functions, diseases, phenotypes and chemicals. (edu.sa)
Disorders9
- citation needed] The disease is one in a group of genetic disorders collectively known as leukodystrophies that affect the growth of the myelin sheath, the fatty covering-which acts as an insulator-on nerve fibers in the central nervous system. (wikipedia.org)
- Information about Pelizaeus-Merzbacher disease is also available from the National Institutes of Health (NIH) at http://www.ninds.nih.gov/disorders/pelizaeus_merzbacher/pelizaeus_merzbacher.htm. (medscape.com)
- [3] The proteinopathies include such diseases as Creutzfeldt-Jakob disease and other prion diseases , Alzheimer's disease , Parkinson's disease , amyloidosis , multiple system atrophy , and a wide range of other disorders. (wikipedia.org)
- I discuss issues pertaining to the practice of neuropathology -- including nervous system tumors, neuroanatomy, neurodegenerative disease, muscle and nerve disorders, ophthalmologic pathology, neuro trivia, neuropathology gossip, job listings and anything else that might be of interest to a blue-collar neuropathologist. (blogspot.com)
- Diseases and Disorders Links pertaining to Central Nervous System Diseases Alert! (geometry.net)
- IMMUNE SYSTEM DISORDERS: Genetic or acquired diseases which result in white blood cells that are not able to fight off infections. (upstatecordbloodbank.com)
- INHERITED METABOLIC DISORDERS: Genetic diseases that prevent the body from correctly processing normal substances in the body or diet. (upstatecordbloodbank.com)
- The discipline encompasses diseases and disorders of the spinal cord, brain, peripheral nervous system, autonomic nervous system, muscles and blood vessels that affect individuals in these age groups. (topneurodocs.com)
- This group includes lysosomal storage disorders, various mitochondrial diseases, other neurometabolic disorders, and several other miscellaneous disorders. (medscape.com)
Demyelinating Diseases1
- Loss of Myelin Basic Protein Function Triggers Myelin Breakdown in Models of Demyelinating Diseases. (unibas.ch)
Myelin7
- It is characterized by a decrease in the amount of insulating myelin surrounding the nerves (hypomyelination) and belongs to a group of genetic diseases referred to as leukodystrophies. (wikipedia.org)
- Correlation Between Anti-Myelin Proteolipid Protein (PLP) Antibodies and Disease Severity in Multiple Sclerosis Patients With PLP Response-Permissive HLA Types. (nih.gov)
- Susceptibility-based imaging aids accurate distinction of pediatric-onset MS from myelin oligodendrocyte glycoprotein antibody-associated disease. (ucsf.edu)
- Myelin loss is at the heart of multiple sclerosis, and also plays a role in the symptoms of diabetes, high blood pressure, and other diseases. (news-medical.net)
- In children, diseases of myelin go by a host of names but share the same features: a childhood and young adulthood that may include weakness, difficulty standing or walking, seizures, dementia, paralysis, and ultimately, death. (news-medical.net)
- Diseases that affect myelin in various areas of the body can lead to either demyelination or dysmyelination. (e-adventure.net)
- This autoimmune disease occurs when the immune system attacks myelin in the central nervous system, leading to damage and inflammation. (e-adventure.net)
Mutation1
- Disease onset, symptoms and mortality span a broad spectrum depending on the nature of the mutation and thus the degree of CNS hypomyelination. (gla.ac.uk)
Hypomyelinating1
- Hypomyelinating leukodystrophy is the main feature of Pelizaeus-Merzbacher disease (PMD) and Pelizaeus-Merzbacher-like disease (PMLD1). (cegat.com)
Phenotypes1
- Phenotype comparisons summarize the similarity of mouse phenotypes with human disease phenotypes. (mousephenotype.org)
Connatal1
- Patients who are severely affected (ie, those who have connatal Pelizaeus-Merzbacher disease) need special attention directed to airway protection and may need anticonvulsant therapy. (medscape.com)
Neurology1
- This year The Jacob's Ladder Norman Saunders International Research Prize, named in memory of Jacob's beloved doctor, recognizes the outstanding work of Mustafa Sahin M.D., Ph.D. Dr. Sahin is a specialist in the field of childhood neurological diseases and currently holds the position of Director, Translational Neuroscience Center and Professor of Neurology, Harvard Medical School. (jacobsladder.ca)
Globoid Cell Leukodyst2
- krabbe disease (also called Globoid Cell Leukodystrophy). (geometry.net)
- krabbe disease (Globoid Cell Leukodystrophy) mini factsheets NINDS. (geometry.net)
Patients4
- Most (8590%) patients with krabbe disease have the infantile form. (geometry.net)
- Cardiologist Aseem Malhotra told a conference that doctors were unwittingly practising "unethical medicine" by prescribing statins which he said offered little or no benefit to patients at low risk of heart disease.He also claimed patients were not being told the true benefits and harms of the cholesterol lowering drug. (infiniteunknown.net)
- Characterisation of breakpoints in patients with apparently balanced constitutional chromosome rearrangements and phenotypic abnormalities has proved an invaluable strategy for identifying disease causing genes, especially those on the X chromosome. (bmj.com)
- Approximately 15% of patients follow a primary progressive or progressive relapsing course from disease onset, usually characterized by symptoms of progressive myelopathy (gait instability, spasticity, bladder symptoms) and cognitive impairment. (medscape.com)
Onset3
- citation needed] The onset of Pelizaeus-Merzbacher disease is usually in early infancy. (wikipedia.org)
- APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy. (nature.com)
- The spectrum of propionic acidemia (PA) ranges from neonatal-onset to late-onset disease. (beds.ac.uk)
Garbern1
- Garbern, J. and Hobson, G. Prenatal diagnosis of Pelizaeus-Merzbacher disease. (centerforpediatricresearch.org)
Krabbe Disease7
- MedicineNet Home MedTerms medical dictionary AZ List krabbe disease. (geometry.net)
- krabbe disease Clinical Resources. (geometry.net)
- krabbe disease Patient/Family Resources. (geometry.net)
- About krabbe disease - OMIM, NCBI (US). (geometry.net)
- What is krabbe disease? (geometry.net)
- krabbe disease is a degenerative disorder that affects the nervous system. (geometry.net)
- How common is krabbe disease? (geometry.net)
Symptoms2
- The hallmark signs and symptoms of Pelizaeus-Merzbacher disease include little or no movement in the arms or legs, respiratory difficulties, and characteristic horizontal movements of the eyes left to right. (wikipedia.org)
- Heart disease symptoms could be warded off most effectively by eating a bowl of porridge everyday, says an expert. (infiniteunknown.net)
Genes1
- In a novel therapeutic study, Nemours Children's researchers are testing morpholino oligos (molecules used to modify the effect of genes) with children exhibiting Pelizaeus Merzbacher disease (PMD). (nemours.org)
Epidemiology2
- DelveInsight's "Pelizaeus-Merzbacher Disease Market Insights, Epidemiology, and Market Forecast-2032" report delivers an in-depth understanding of the Pelizaeus-Merzbacher Disease, historical and forecasted epidemiology as well as the Pelizaeus-Merzbacher Disease market trends in the United States, EU5 (Germany, Spain, Italy, France, and United Kingdom) and Japan. (southdakotachronicle.com)
- DelveInsight's " Pelizaeus-Merzbacher Disease Market Insights, Epidemiology, and Market Forecast-2032 " report delivers an in-depth understanding of the Merkel Cell Carcinoma, epidemiology insights, Merkel Cell Carcinoma market trends, therapies, and key companies working in the Merkel Cell Carcinoma Market in the 7MM. (southdakotachronicle.com)
Sclerosis6
- This disease has a progressive and almost unvarying course, which is the clinical key to differentiating it from other entities such as infantile cerebral palsy, peripheral neuropathies or multiple sclerosis, etc. (medscape.com)
- The Pelizaeus Merzbacher Disease Support Group is for families within the United Kingdom affected by Pelizaeus Merzbacher disease, sometimes called Pelizaeus Merzbacher brain sclerosis or PMD. (rarediseases.org)
- Inflammatory and neurodegenerative serum protein biomarkers increase sensitivity to detect disease activity in multiple sclerosis. (ucsf.edu)
- What we learn will also have broad implications for other diseases that affect nerve cells' ability to conduct signals, such as cerebral palsy and multiple sclerosis. (nemours.org)
- Multiple sclerosis is a common, chronic demyelinating neurological disease primarily affecting young adults, with a prevalence of ~0.1% in the Caucasian population (Miller and Leary, 2007). (medscape.com)
- Diagnostic criteria and classification of multiple sclerosis subtypes have evolved in recent decades, and, although successive versions have differed in emphasis, all have required dissemination of disease in space (requiring involvement of multiple areas of the CNS) and in time (requiring ongoing disease activity over time). (medscape.com)
Brain4
- This is a rare inherited disease that affects the central nervous system and is associated with abnormalities of the white matter of the brain. (rarediseases.org)
- Huntington's disease is a condition that stops parts of the brain working properly over time. (cam.ac.uk)
- Parkinson's disease is a condition in which part of the brain become progressively damaged over many years. (cam.ac.uk)
- Parkinson's disease is caused by a loss of nerve cells in a part of the brain called the substantia nigra. (cam.ac.uk)
Congenital2
Infancy1
- The Context: Pelizaeus - Merzbacher disease (PMD) is a rare neurological condition typically diagnosed in infancy which often becomes fatal by a patient's teenage years. (nyscf.org)
Severe3
- This causes hypomyelination in the central nervous system and severe neurological disease. (wikipedia.org)
- Outcomes are variable: people with the most severe form of the disease do not usually survive to adolescence, although with milder forms, survival into adulthood is possible. (wikipedia.org)
- Severe Pelizaeus-Merzbacher disease is often fatal during the first decade of life, typically due to respiratory complications. (medscape.com)
Protein4
- Misalignment of PLP/DM20 transmembrane domains determines protein misfolding in Pelizaeus-Merzbacher disease. (medscape.com)
- Micrograph of a section of the cerebral cortex from a person with Alzheimer's disease , immunostained with an antibody to amyloid beta (brown), a protein fragment that accumulates in amyloid plaques and cerebral amyloid angiopathy . (wikipedia.org)
- proteinopathic adj ), or proteopathy , protein conformational disorder , or protein misfolding disease , is a class of diseases in which certain proteins become structurally abnormal, and thereby disrupt the function of cells , tissues and organs of the body. (wikipedia.org)
- [20] They have been most thoroughly studied with regard to prion disease , and are referred to as protein strains . (wikipedia.org)
Neurodegenerative disease1
- First patient-derived, induced pluripotent stem cell disease-specific organoid models in microgravity to advance understanding of neurodegenerative disease LOUISVILLE, KY - (BUSINESS WIRE) - The National Stem. (nyscf.org)
Adult1
- More research teams are accelerating the use of other types of adult stem cells, in particular neural stem cells for diseases where beneficial outcome could result from either in-lineage cell replacement or extracellular factors. (biomedcentral.com)
Fatal1
- Scientists have used human stem cells to dramatically improve the condition of mice with a neurological condition similar to a set of diseases in children that are invariably fatal, according to an article in the June issue of the journal Cell Stem Cell. (news-medical.net)
Stroke1
- That abdominal fat, sometimes described as making people apple-shaped rather than pear-shaped, has already been linked to higher risk of developing diabetes, stroke and heart disease. (blogspot.com)
Syndrome2
- Zellweger Syndrome Central Nervous System Diseases Nerve Cells [Lodish et al. (geometry.net)
- Although Alzheimer disease (AD) is more frequent in individuals with Down syndrome (DS), the main contributing factor is unknown. (medscape.com)
Disorder3
- Pelizaeus-Merzbacher disease is an X-linked neurological disorder that damages oligodendrocytes in the central nervous system. (wikipedia.org)
- NORD is not a medical provider or health care facility and thus can neither diagnose any disease or disorder nor endorse or recommend any specific medical treatments. (rarediseases.org)
- Pelizaeus-Merzbacher disease (PMD) is a rare, progressive, and degenerative central nervous system disorder that deteriorates coordination, motor abilities, and cognitive function. (southdakotachronicle.com)
Abnormalities2
- INHERITED RED CELL ABNORMALITIES: Genetic diseases resulting in red blood cells that do not work correctly. (upstatecordbloodbank.com)
- INHERITED PLATELET ABNORMALITIES: Genetic diseases resulting in platelets that are not able to correctly form clots. (upstatecordbloodbank.com)
Neurological diseases2
- The work marks an important step toward the day when stem cells become an option for the treatment of neurological diseases in people. (news-medical.net)
- Dr. Bernard Brais is a neurologist, co-director of the Rare Neurological Diseases group of the Montreal Neurological Institute and Hospital. (jacobsladder.ca)
Getting Alzheimer's disease1
- The revered Dr. Michael Beckman sent me a recently published Associated Press article by Malcom Ritter on research suggesting that "having a big belly in your 40s can boost your risk of getting Alzheimer's disease or other dementia decades later. (blogspot.com)
Nervous system1
- It's extremely exciting to think about not only treating but actually curing a disease, particularly an awful disease that affects children," said neurologist Steven Goldman, M.D., Ph.D., a leader in manipulating stem cells to treat diseases of the nervous system. (news-medical.net)
Diagnosis2
- citation needed] The diagnosis of Pelizaeus-Merzbacher disease is often first suggested after identification by magnetic resonance imaging of abnormal white matter (high T2 signal intensity, i.e. (wikipedia.org)
- They found that Forex positions SPECT, CT, and MRI were equally sensitive (8792) and specific (8894) for the diagnosis of pyelonephritis in 38 kidneys with 102 zones of disease. (top5binarybrokers.com)
20192
- In 2019 Paul Tesar, a professor at Case Western Reserve University, used CRISPR and antisense therapy in a mouse model of Pelizaeus-Merzbacher with success. (wikipedia.org)
- According to DelveInsight, the Pelizaeus-Merzbacher Disease market in 7MM is expected to witness a major change in the study period 2019-2032. (southdakotachronicle.com)
Rare diseases7
- From the outset the idea and motivation of The Captain's Ride has been clear - to raise significant funds for the Foundation, increase awareness about rare diseases and the bravery of the kids who live with them, and in some way replicated the challenges that our kids and families go through each and every day. (stevewaughfoundation.com.au)
- Our target is to raise significant funds for the Steve Waugh Foundationto champion the stories of and provide life changing support to children and young adults affected by a rare diseases. (stevewaughfoundation.com.au)
- 8,000 known rare diseases. (stevewaughfoundation.com.au)
- Rare Disease PHGKB is an online, continuously updated, searchable database of published scientific literature, CDC and NIH resources, and other information that address the public health impact and translation of genomic and other precision health discoveries into improved health outcomes related to rare diseases. (cdc.gov)
- The Global Journal of Rare Diseases welcome manuscripts on new researches, interesting discoveries related to the rare disease community. (peertechzpublications.org)
- Peertechz appeals the authors to play a distinctive role in putting forward rare diseases as a much needed public health priority world-wide. (peertechzpublications.org)
- The Global Journal of Rare Diseases urges the prominent researchers, intensive writers and workaholic doctors to publish breakthrough manuscripts with Peertechz that can lead the way to studies leading to education, research and advocacy towards patient services to improve the lives of all people living with rare diseases. (peertechzpublications.org)
OMIM1
- The analysis uses data from IMPC, along with published data on other mouse mutants, in comparison to human disease reports in OMIM, Orphanet, and DECIPHER. (mousephenotype.org)
Prognosis1
- The prognosis is poor as no treatment is available for the primary disease. (medscape.com)
Stem cells1
- Our researchers are working across the disease spectrums to harness the therapeutic potential of stem cells. (cam.ac.uk)