PMD
MCID: PLZ001
MIFTS: 64

Pelizaeus-Merzbacher Disease (PMD)

Categories: Eye diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Pelizaeus-Merzbacher Disease

MalaCards integrated aliases for Pelizaeus-Merzbacher Disease:

Name: Pelizaeus-Merzbacher Disease 56 12 74 52 25 53 58 73 73 29 13 54 6 43 15 37 39 71
Pmd 56 12 52 25 58 73
Hld1 56 12 25 73
Pelizaeus-Merzbacher Brain Sclerosis 12 58 73
Sudanophilic Leukodystrophy, Paelizeus-Merzbacher Type 12 58
Cockayne-Pelizaeus-Merzbacher Disease 25 71
Pelizaeus Merzbacher Brain Sclerosis 12 52
Leukodystrophy, Hypomyelinating, 1 56 73
Diffuse Familial Brain Sclerosis 12 58
Sudanophilic Leukodystrophy Paelizeus-Merzbacher Type 73
Pelizaeus-Merzbacher Disease, Connatal Form 58
Pelizaeus-Merzbacher Disease, Null Syndrome 58
Leukodystrophy, Hypomyelinating, 1; Hld1 56
Diffuse Cerebral Sclerosis of Schilder 71
Pelizaeus-Merzbacher Disease Type Ii 58
Hypomyelinating Leukodystrophy, 1 25
Hypomyelinating Leukodystrophy 1 12
Brain Sclerosis Diffuse Familial 73
Leukodystrophy Hypomyelinating 1 73
Leukodystrophy, Sudanophilic 12
Pelizaeus Merzbacher Disease 52
Sudanophilic Leukodystrophy 25
Plp1 Null Syndrome 58
Null Syndrome 58
Connatal Pmd 58
Severe Pmd 58

Characteristics:

Orphanet epidemiological data:

58
pelizaeus-merzbacher disease
Inheritance: X-linked dominant,X-linked recessive; Prevalence: 1-9/1000000 (Europe); Age of onset: All ages;
pelizaeus-merzbacher disease, connatal form
Inheritance: X-linked recessive; Prevalence: <1/1000000 (Europe); Age of onset: Infancy,Neonatal; Age of death: any age;
null syndrome
Inheritance: X-linked recessive; Age of onset: Childhood; Age of death: adult;

OMIM:

56
Miscellaneous:
onset in infancy
slowly progressive
nystagmus may disappear by mid-childhood
hearing impairment may improve with age
connatal form (type ii), most severe with death in first decade
classical form (type i), less severe with survival into adulthood
spastic paraplegia 2 (spg2, ) is an allelic disorder

Inheritance:
x-linked recessive


HPO:

31
pelizaeus-merzbacher disease:
Onset and clinical course infantile onset slow progression
Inheritance x-linked recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases


Summaries for Pelizaeus-Merzbacher Disease

Genetics Home Reference : 25 Pelizaeus-Merzbacher disease is an inherited condition involving the brain and spinal cord (central nervous system) that primarily affects males. This disease is one of a group of genetic disorders called leukodystrophies. Leukodystrophies are conditions that involve abnormalities of the nervous system's white matter, which consists of nerve fibers covered by a fatty substance called myelin. Myelin insulates nerve fibers and promotes the rapid transmission of nerve impulses. In particular, Pelizaeus-Merzbacher disease involves hypomyelination, which means that the nervous system has a reduced ability to form myelin. As a result, overall neurological function is reduced. Pelizaeus-Merzbacher disease is divided into classic and connatal (present from birth) types. Although these two types differ in severity, their features can overlap. Classic Pelizaeus-Merzbacher disease is the more common type. Within the first year of life, those affected with classic Pelizaeus-Merzbacher disease typically experience weak muscle tone (hypotonia), involuntary movements of the eyes (nystagmus), and delayed development of motor skills, such as sitting or grasping objects. Some individuals are able to walk with assistance. Despite these neurological problems, intellectual and motor skills develop throughout childhood, but development usually stops around adolescence, and these skills are slowly lost (developmental regression). As the condition worsens, nystagmus usually goes away but other movement disorders develop, including muscle stiffness (spasticity), problems with movement and balance (ataxia), head and neck tremors (titubation), involuntary tensing of the muscles (dystonia), and jerking (choreiform) movements. Connatal Pelizaeus-Merzbacher disease is the more severe of the two types. Symptoms can begin in infancy and include problems with feeding, poor weight gain and slow growth, high-pitched breathing caused by an obstructed airway (stridor), nystagmus, progressive speech difficulties (dysarthria), severe ataxia, hypotonia, and seizures. As the condition worsens, affected children develop spasticity leading to joint deformities (contractures) that restrict movement. Individuals with connatal Pelizaeus-Merzbacher disease are never able to walk, and many are not able to purposefully use their arms. They also have problems producing speech (expressive language) but can generally understand speech (receptive language).

MalaCards based summary : Pelizaeus-Merzbacher Disease, also known as pmd, is related to leukodystrophy, hypomyelinating, 2 and pelizaeus-merzbacher-like disease, and has symptoms including seizures, ataxia and scanning speech. An important gene associated with Pelizaeus-Merzbacher Disease is PLP1 (Proteolipid Protein 1), and among its related pathways/superpathways are Neural Crest Differentiation and Validated targets of C-MYC transcriptional activation. The drugs Prednisolone phosphate and Methylprednisolone have been mentioned in the context of this disorder. Affiliated tissues include Brain and Spinal Cord, and related phenotypes are nystagmus and psychomotor deterioration

Disease Ontology : 12 A hypomyelinating leukodystrophy characterized by impaired myelin formation, nystagmus, spastic quadriplegia, ataxia, and developmental delay that has material basis in mutation in the PLP1 gene on chromosome Xq22.

NIH Rare Diseases : 52 Pelizaeus-Merzbacher disease is a disorder that affects the brain and spinal cord. It is a type of leukodystrophy and is characterized by problems with coordination, motor skills, and learning. The age of onset and the severity of the symptoms varies greatly depending on the type of disease. It is caused by an inability to form myelin due to mutations in the PLP1 gene . It is passed through families in an X-linked recessive pattern. The condition primarily affects males. Treatment requires a multidisciplinary team approach, with members dictated by the presenting symptoms.

OMIM : 56 Pelizaeus-Merzbacher disease is an X-linked recessive hypomyelinative leukodystrophy (HLD1) in which myelin is not formed properly in the central nervous system. PMD is characterized clinically by nystagmus, spastic quadriplegia, ataxia, and developmental delay (Inoue, 2005). (312080)

NINDS : 53 Pelizaeus-Merzbacher disease (PMD) is a rare, progressive, degenerative central nervous system disorder in which coordination, motor abilities, and intellectual function deteriorate. The disease is one of a group of gene-linked disorders known as the leukodystrophies, which affect growth of the myelin sheath -- the fatty covering that wraps around and protects nerve fibers in the brain. The disease is caused by a mutation in the gene that controls the production of a myelin protein called proteolipid protein-1 (PLP1). PMD is inherited as an X-linked recessive trait; the affected individuals are male and the mothers are carriers of the PLP1 mutation. Severity and onset of the disease ranges widely, depending on the type of PLP1 mutation. PMD is one of a spectrum of diseases associated with PLP1, which also includes Spastic Paraplegia Type 2 (SPG2). The PLP1-related disorders span a continuum of neurologic symptoms that range from severe central nervous system involvement (PMD) to progressive weakness and stiffness of the legs (SPG2). There are four general classifications within this spectrum of diseases. In order of severity, they are: Connatal PMD, which is the most severe type and involves delayed mental and physical development and severe neurological symptoms; Classic PMD, in which the early symptoms include muscle weakness, involuntary movements of the eyes (nystagmus), and delays in motor development within the first year of life; Complicated SPG2, which features motor development issues and brain involvement, and, Pure SPG2, which includes cases of PMD that do not have neurologic complications. Noticeable changes in the extent of myelination can be detected by MRI analyses of the brain. Additional symptoms of PMD may include slow growth, tremor, failure to develop normal control of head movement, and deteriorating speech and cognitive function.

UniProtKB/Swiss-Prot : 73 Leukodystrophy, hypomyelinating, 1: An X-linked recessive disorder of the central nervous system in which myelin is not formed properly. Clinically characterized by nystagmus, spastic quadriplegia, ataxia, and developmental delay.
Pelizaeus-Merzbacher disease: An X-linked recessive hypomyelinating disorder of the central nervous system in which myelin is not formed properly. PMD is characterized clinically by nystagmus, spastic quadriplegia, ataxia, and developmental delay.

Wikipedia : 74 Pelizaeus-Merzbacher disease is an X-linked neurological disorder that damages oligodendrocytes in the... more...

Related Diseases for Pelizaeus-Merzbacher Disease

Diseases in the Pelizaeus-Merzbacher Disease family:

Pelizaeus-Merzbacher-Like Disease

Diseases related to Pelizaeus-Merzbacher Disease via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 261)
# Related Disease Score Top Affiliating Genes
1 leukodystrophy, hypomyelinating, 2 34.1 PLP1 MBP GJC2
2 pelizaeus-merzbacher-like disease 33.9 PLP1 GJC2
3 leukodystrophy 33.8 SERPINA3 RARS1 PLP1 MPZ MAG GJC2
4 hypomyelinating leukodystrophy 32.5 SERPINA3 PRDM10 PMVK PLP1 MYCBP2 MVK
5 spastic quadriplegia 31.6 RAB9B PLP1 ERCC6
6 demyelinating disease 31.5 SERPINA3 PMP22 PLP1 MPZ MBP MAG
7 spastic paraplegia 75, autosomal recessive 31.5 PLP1 MAG GJC2
8 leukodystrophy, hypomyelinating, 9 31.4 RARS1 GJC2 ERCC6
9 neuropathy, hereditary, with liability to pressure palsies 31.4 PMP22 MPZ MAG
10 hypomyelinating leukoencephalopathy 31.3 PLP1 GJC2
11 hereditary neuropathies 31.3 PMP22 PLP1 MPZ MBP MAG
12 autosomal recessive disease 31.3 SERPINA3 PRDM10 MVK H2AC18 ERCC6
13 central nervous system disease 31.1 SERPINA3 PLP1 MBP H2AC18 ERCC6
14 distal arthrogryposis 30.9 SERPINA3 PRDM10 HUWE1 H2AC18 GAPDH ACTB
15 peripheral nervous system disease 30.9 SERPINA3 PRDM10 PMP22 MPZ MBP MAG
16 x-linked recessive disease 30.9 SERPINA3 PRDM10 PLP1 H2AC18 GAPDH ERCC6
17 charcot-marie-tooth disease 30.8 PRDM10 PMP22 PLP1 MPZ MBP MAG
18 polyneuropathy 30.2 PMP22 MPZ MBP MAG
19 pelizaeus-merzbacher disease, classic form 12.7
20 pelizaeus-merzbacher disease, transitional form 12.7
21 cerebral sclerosis similar to pelizaeus-merzbacher disease 12.6
22 pelizaeus-merzbacher disease in female carriers 12.6
23 leukodystrophy, demyelinating, adult-onset, autosomal dominant 12.2
24 spastic paraplegia 2, x-linked 12.1
25 leukodystrophy, hypomyelinating, 3 11.9
26 retinohepatoendocrinologic syndrome 11.9
27 microphthalmia, syndromic 9 11.8
28 autosomal dominant leukodystrophy with autonomic disease 11.6
29 persistent mullerian duct syndrome, types i and ii 11.4
30 rh-null, amorph type 11.2
31 pellucid marginal degeneration 11.2
32 pathologic nystagmus 11.2
33 paraplegia 11.0
34 plp1 disorders 11.0
35 spasticity 11.0
36 hypotonia 10.9
37 ataxia and polyneuropathy, adult-onset 10.9
38 cerebral palsy 10.8
39 tremor 10.7
40 quadriplegia 10.7
41 allergic encephalomyelitis 10.7 PLP1 MBP
42 niemann-pick disease 10.7 PLP1 MBP MAG
43 foot drop 10.7 PMP22 MPZ
44 central pontine myelinolysis 10.6 MBP MAG GJC2
45 charcot-marie-tooth disease type x 10.6 PMP22 MPZ GJC2
46 leukodystrophy, hypomyelinating, 5 10.6 PLP1 GJC2 ERCC6
47 autoimmune neuropathy 10.6 PMP22 MPZ MAG
48 charcot-marie-tooth disease, x-linked dominant, 1 10.6 PMP22 MPZ GJC2
49 mononeuropathy 10.6 PMP22 MPZ MAG
50 chronic inflammatory demyelinating polyradiculoneuropathy 10.6 PMP22 MPZ MBP

Graphical network of the top 20 diseases related to Pelizaeus-Merzbacher Disease:



Diseases related to Pelizaeus-Merzbacher Disease

Symptoms & Phenotypes for Pelizaeus-Merzbacher Disease

Human phenotypes related to Pelizaeus-Merzbacher Disease:

58 31 (show top 50) (show all 52)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 nystagmus 58 31 obligate (100%) Very frequent (99-80%) HP:0000639
2 psychomotor deterioration 31 obligate (100%) HP:0002361
3 behavioral abnormality 58 31 hallmark (90%) Very frequent (99-80%) HP:0000708
4 muscular hypotonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001252
5 scoliosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0002650
6 kyphosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0002808
7 joint stiffness 58 31 hallmark (90%) Very frequent (99-80%) HP:0001387
8 visual impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0000505
9 optic atrophy 58 31 frequent (33%) Very frequent (99-80%) HP:0000648
10 developmental regression 58 31 hallmark (90%) Very frequent (99-80%) HP:0002376
11 gait disturbance 58 31 hallmark (90%) Very frequent (99-80%) HP:0001288
12 spasticity 58 31 hallmark (90%) Very frequent (99-80%) HP:0001257
13 ataxia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001251
14 cachexia 58 31 hallmark (90%) Very frequent (99-80%) HP:0004326
15 failure to thrive in infancy 58 31 hallmark (90%) Very frequent (99-80%) HP:0001531
16 cerebral cortical atrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0002120
17 dystonia 58 31 hallmark (90%) Frequent (79-30%) HP:0001332
18 premature birth 58 31 hallmark (90%) Very frequent (99-80%) HP:0001622
19 global developmental delay 31 hallmark (90%) HP:0001263
20 abnormal pyramidal sign 31 hallmark (90%) HP:0007256
21 progressive spastic quadriplegia 31 hallmark (90%) HP:0002478
22 hearing impairment 58 31 occasional (7.5%) Frequent (79-30%) HP:0000365
23 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
24 recurrent respiratory infections 58 31 frequent (33%) Frequent (79-30%) HP:0002205
25 neurological speech impairment 58 31 frequent (33%) Frequent (79-30%) HP:0002167
26 microcephaly 58 31 frequent (33%) Frequent (79-30%) HP:0000252
27 short stature 58 31 frequent (33%) Frequent (79-30%) HP:0004322
28 abnormality of visual evoked potentials 58 31 frequent (33%) Frequent (79-30%) HP:0000649
29 arteriovenous malformation 58 31 frequent (33%) Frequent (79-30%) HP:0100026
30 bowel incontinence 58 31 frequent (33%) Frequent (79-30%) HP:0002607
31 respiratory insufficiency 58 31 frequent (33%) Frequent (79-30%) HP:0002093
32 abnormality of the urinary system 58 31 frequent (33%) Frequent (79-30%) HP:0000079
33 choreoathetosis 58 31 frequent (33%) Frequent (79-30%) HP:0001266
34 delayed speech and language development 31 frequent (33%) HP:0000750
35 failure to thrive 31 frequent (33%) HP:0001508
36 dysphagia 31 frequent (33%) HP:0002015
37 dysarthria 31 frequent (33%) HP:0001260
38 head titubation 31 frequent (33%) HP:0002599
39 seizure 31 occasional (7.5%) HP:0001250
40 sudanophilic leukodystrophy 31 frequent (33%) HP:0003269
41 reduction of oligodendroglia 31 frequent (33%) HP:0100709
42 peripheral neuropathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0009830
43 congenital laryngeal stridor 31 occasional (7.5%) HP:0004886
44 hyporeflexia 31 very rare (1%) HP:0001265
45 seizures 58 Frequent (79-30%)
46 tremor 31 HP:0001337
47 abnormality of movement 58 Very frequent (99-80%)
48 leukodystrophy 31 HP:0002415
49 scanning speech 31 HP:0002168
50 generalized hypotonia 31 HP:0001290

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
seizures
spasticity
ataxia
dysarthria
dystonia
more
Head And Neck Eyes:
optic atrophy
rotary nystagmus

Growth:
developmental delay

Head And Neck Head:
microcephaly

Respiratory Larynx:
stridor

Head And Neck Ears:
hearing impairment (in some patients)
decreased or absent brainstem auditory evoked potentials (baep) of waves iii-v

Clinical features from OMIM:

312080

UMLS symptoms related to Pelizaeus-Merzbacher Disease:


seizures, ataxia, scanning speech, stridor, muscle spasticity

GenomeRNAi Phenotypes related to Pelizaeus-Merzbacher Disease according to GeneCards Suite gene sharing:

26 (show all 11)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00221-A-1 9.7 PMVK
2 Decreased viability GR00221-A-2 9.7 PMVK
3 Decreased viability GR00221-A-4 9.7 PMVK
4 Decreased viability GR00249-S 9.7 GAPDH HMGA1 MPZ PDE3B PMVK SERPINA3
5 Decreased viability GR00342-S-1 9.7 PMVK
6 Decreased viability GR00342-S-2 9.7 PMVK
7 Decreased viability GR00342-S-3 9.7 PMVK
8 Decreased viability GR00381-A-1 9.7 ACTB MPZ PRDM10
9 Decreased viability GR00381-A-3 9.7 MPZ
10 Decreased viability GR00386-A-1 9.7 ERCC6 MPZ RAB9B
11 Decreased viability GR00402-S-2 9.7 ACTB MBP MPZ RAB9B RARS1

MGI Mouse Phenotypes related to Pelizaeus-Merzbacher Disease:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.03 ACTB ERCC6 GJC2 MAG MBP MPZ
2 growth/size/body region MP:0005378 9.97 ACTB ERCC6 GAPDH HMGA1 HUWE1 MBP
3 mortality/aging MP:0010768 9.77 ACTB ERCC6 GAPDH GJC2 HMGA1 HUWE1
4 nervous system MP:0003631 9.36 ACTB ERCC6 GJC2 HUWE1 MAG MBP

Drugs & Therapeutics for Pelizaeus-Merzbacher Disease

Drugs for Pelizaeus-Merzbacher Disease (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 7)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Prednisolone phosphate Approved, Vet_approved Phase 3 302-25-0
2
Methylprednisolone Approved, Vet_approved Phase 3 83-43-2 6741
3
Methylprednisolone hemisuccinate Approved Phase 3 2921-57-5
4 Prednisolone acetate Approved, Vet_approved Phase 3 52-21-1
5
Prednisolone Approved, Vet_approved Phase 3 50-24-8 5755
6
Prednisolone hemisuccinate Experimental Phase 3 2920-86-7
7 Methylprednisolone Acetate Phase 3

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Phase III Randomized, Double-Blind, Sham-Controlled Study of Plasma Exchange for Acute Severe Attacks of Inflammatory Demyelinating Disease Refractory to Intravenous Methylprednisolone Unknown status NCT00004645 Phase 3
2 Phase I Study of the Safety and Preliminary Efficacy of Intracerebral Transplantation of HuCNS-SC® Cells for Connatal Pelizaeus-Merzbacher Disease (PMD) Completed NCT01005004 Phase 1
3 Augmentation of Umbilical Cord Blood Transplantation for Inherited Metabolic Diseases With Intrathecal Administration of Human Umbilical Cord Blood-Derived Oligodendrocyte-Like Cells Recruiting NCT02254863 Phase 1
4 Treatment of Early Infantile-Onset Lysosomal Storage Diseases With Fetal Umbilical Cord Blood (UCB) Transplantation Withdrawn NCT01003912 Phase 1
5 Long-Term Follow-Up Safety and Preliminary Efficacy Study of Human Central Nervous System Stem Cell (HuCNS-SC®) Transplantation in Subjects With Connatal Pelizaeus-Merzbacher Disease (PMD) Completed NCT01391637
6 Longitudinal Study of Neurodegenerative Disorders Recruiting NCT03333200
7 Natural History Study of Alpers Huttenlocher Syndrome Recruiting NCT03034512

Search NIH Clinical Center for Pelizaeus-Merzbacher Disease

Cell-based therapeutics:


LifeMap Discovery
Data from LifeMap, the Embryonic Development and Stem Cells Database
Read about Pelizaeus-Merzbacher Disease cell therapies at LifeMap Discovery.
Stem-cell-based therapeutic approaches for Pelizaeus-Merzbacher Disease:
Enriched hematopoetic stem cell for inherited metabolic disorders
HuCNS-SC, human central nervous system stem cells for neurological diseases
Embryonic/Adult Cultured Cells Related to Pelizaeus-Merzbacher Disease:
Bone marrow-derived hematopoietic stem cells (family) PMIDs: 22430083
Human neural stem cells (HuCNS-SC) PMIDs: 16610769

Cochrane evidence based reviews: pelizaeus-merzbacher disease

Genetic Tests for Pelizaeus-Merzbacher Disease

Genetic tests related to Pelizaeus-Merzbacher Disease:

# Genetic test Affiliating Genes
1 Pelizaeus-Merzbacher Disease 29 PLP1

Anatomical Context for Pelizaeus-Merzbacher Disease

MalaCards organs/tissues related to Pelizaeus-Merzbacher Disease:

40
Brain, Eye, Spinal Cord, Bone, Cerebellum, Lung, Thyroid
LifeMap Discovery
Data from LifeMap, the Embryonic Development and Stem Cells Database

Cells/anatomical compartments in embryo or adult related to Pelizaeus-Merzbacher Disease:
# Tissue Anatomical CompartmentCell Relevance
1 Brain Forebrain White Matter Myelinating Oligodendrocyte Cells Affected by disease
2 Spinal Cord Spinal Cord White Matter Myelinating Oligodendrocyte Cells Affected by disease

Publications for Pelizaeus-Merzbacher Disease

Articles related to Pelizaeus-Merzbacher Disease:

(show top 50) (show all 548)
# Title Authors PMID Year
1
A duplicated PLP gene causing Pelizaeus-Merzbacher disease detected by comparative multiplex PCR. 54 61 56 6
8659540 1996
2
Complete deletion of the proteolipid protein gene (PLP) in a family with X-linked Pelizaeus-Merzbacher disease. 54 61 6 56
1720927 1991
3
Pelizaeus-Merzbacher disease: identification of Xq22 proteolipid-protein duplications and characterization of breakpoints by interphase FISH. 61 56 6
9634530 1998
4
Pelizaeus-Merzbacher disease: tight linkage to proteolipid protein gene exon variant. 61 6 56
2480601 1989
5
Mutation of the proteolipid protein gene PLP in a human X chromosome-linked myelin disorder. 6 56 61
2479017 1989
6
Pelizaeus-Merzbacher disease: an X-linked neurologic disorder of myelin metabolism with a novel mutation in the gene encoding proteolipid protein. 56 6 61
2773936 1989
7
Defective biosynthesis of proteolipid protein in Pelizaeus-Merzbacher disease. 61 56 6
3827224 1987
8
Arena syndrome is caused by a missense mutation in PLP1. 6 56
19396823 2009
9
Spastic paraplegia with iron deposits in the basal ganglia: a new X-linked mental retardation syndrome. 56 6
1605230 1992
10
Genotype-phenotype correlation in five Pelizaeus-Merzbacher disease patients with PLP1 gene duplications. 56 61 54
18190592 2008
11
Pelizaeus-Merzbacher syndrome: neurocognitive function in a family with carrier manifestations. 54 56 61
17568416 2007
12
Heterogeneous duplications in patients with Pelizaeus-Merzbacher disease suggest a mechanism of coupled homologous and nonhomologous recombination. 54 61 6
16380909 2005
13
Quantitative proton MRS of Pelizaeus-Merzbacher disease: evidence of dys- and hypomyelination. 61 56 54
16157902 2005
14
Complex chromosomal rearrangement and associated counseling issues in a family with Pelizaeus-Merzbacher disease. 6 54 61
12605435 2003
15
Proteolipoprotein gene analysis in 82 patients with sporadic Pelizaeus-Merzbacher Disease: duplications, the major cause of the disease, originate more frequently in male germ cells, but point mutations do not. The Clinical European Network on Brain Dysmyelinating Disease. 54 61 56
10417279 1999
16
Prenatal diagnosis by FISH in a family with Pelizaeus-Merzbacher disease caused by duplication of PLP gene. 54 56 61
10210128 1999
17
Duplication of the proteolipid protein gene is the major cause of Pelizaeus-Merzbacher disease. 61 54 6
9633722 1998
18
A cellular mechanism governing the severity of Pelizaeus-Merzbacher disease. 56 61 54
8696336 1996
19
Overexpression of DM20 messenger RNA in two brothers with Pelizaeus-Merzbacher disease. 54 6 61
7574457 1995
20
Dominant-negative action of the jimpy mutation in mice complemented with an autosomal transgene for myelin proteolipid protein. 54 61 56
7538670 1995
21
Girl with signs of Pelizaeus-Merzbacher disease heterozygous for a mutation in exon 2 of the proteolipid protein gene. 56 54 61
7539211 1995
22
Premature arrest of myelin formation in transgenic mice with increased proteolipid protein gene dosage. 56 54 61
7512350 1994
23
Pelizaeus-Merzbacher disease: detection of mutations Thr181----Pro and Leu223----Pro in the proteolipid protein gene, and prenatal diagnosis. 61 6 54
1384324 1992
24
Uncoupling of hypomyelination and glial cell death by a mutation in the proteolipid protein gene. 54 61 56
1380672 1992
25
A new mutation in the proteolipid protein (PLP) gene in a German family with Pelizaeus-Merzbacher disease. 61 6 54
1707231 1991
26
Progesterone antagonist therapy in a Pelizaeus-Merzbacher mouse model. 56 61
24680886 2014
27
Depletion of molecular chaperones from the endoplasmic reticulum and fragmentation of the Golgi apparatus associated with pathogenesis in Pelizaeus-Merzbacher disease. 56 61
23344956 2013
28
Evidence for disease penetrance relating to CNV size: Pelizaeus-Merzbacher disease and manifesting carriers with a familial 11 Mb duplication at Xq22. 61 56
21623770 2012
29
The burden of inherited leukodystrophies in children. 56 61
20660364 2010
30
Clinical neurophysiology in GJA12-related hypomyelination vs Pelizaeus-Merzbacher disease. 61 56
20513814 2010
31
Quantifying the carrier female phenotype in Pelizaeus-Merzbacher disease. 56 61
16778599 2006
32
Primary progressive multiple sclerosis as a phenotype of a PLP1 gene mutation. 56 61
16130097 2005
33
PLP1-related inherited dysmyelinating disorders: Pelizaeus-Merzbacher disease and spastic paraplegia type 2. 61 56
15627202 2005
34
The unfolded protein response modulates disease severity in Pelizaeus-Merzbacher disease. 61 56
12441049 2002
35
Compensating for central nervous system dysmyelination: females with a proteolipid protein gene duplication and sustained clinical improvement. 56 61
11761472 2001
36
Genotype-phenotype correlation in inherited brain myelination defects due to proteolipid protein gene mutations. Clinical European Network on Brain Dysmyelinating Disease. 61 56
11093273 2000
37
Mutations in noncoding regions of the proteolipid protein gene in Pelizaeus-Merzbacher disease. 61 6
11071483 2000
38
PLP1 Disorders 61 6
20301361 1999
39
Pelizaeus-Merzbacher disease caused by a de novo mutation that originated in exon 2 of the maternal great-grandfather of the propositus. 6 61
7573159 1995
40
Pelizaeus-Merzbacher disease presenting as spinal muscular atrophy: clinical and molecular studies. 56 61
7998780 1994
41
Genetic homogeneity of Pelizaeus-Merzbacher disease: tight linkage to the proteolipoprotein locus in 16 affected families. PMD Clinical Group. 61 56
7915877 1994
42
Genetics of Pelizaeus-Merzbacher disease. 56 61
7530633 1993
43
Molecular diagnostics for myelin proteolipid protein gene mutations in Pelizaeus-Merzbacher disease. 6 61
1376966 1992
44
Pelizaeus-Merzbacher disease: clinical and DNA-linkage study of an extended family. 56 61
1789292 1991
45
Pelizaeus-Merzbacher disease: a valine to phenylalanine point mutation in a putative extracellular loop of myelin proteolipid. 6 61
1715570 1991
46
Carrier detection and prenatal diagnosis of Pelizaeus-Merzbacher disease using a combination of anonymous DNA polymorphisms and the proteolipid protein (PLP) gene cDNA. 56 61
1676565 1991
47
The otolaryngologic manifestations of Pelizaeus-Merzbacher disease. 56 61
2328119 1990
48
Pelizaeus-Merzbacher disease: identification of heterozygotes with magnetic resonance imaging? 61 56
3198119 1988
49
Comparative immunocytochemistry of Pelizaeus-Merzbacher disease, the jimpy mouse, and the myelin-deficient rat. 56 61
2454299 1988
50
An interstitial duplication of the X chromosome in a male allows physical fine mapping of probes from the Xq13-q22 region. 56 61
3476455 1987

Variations for Pelizaeus-Merzbacher Disease

ClinVar genetic disease variations for Pelizaeus-Merzbacher Disease:

6 (show all 35) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PLP1 NM_000533.5(PLP1):c.175G>T (p.Glu59Ter)SNV Pathogenic 397513 rs1060499653 X:103040681-103040681 X:103785752-103785752
2 PLP1 NM_000533.5(PLP1):c.384_393del (p.Gln129fs)deletion Pathogenic 431701 rs1556267215 X:103041586-103041595 X:103786657-103786666
3 PLP1 NM_000533.5(PLP1):c.453+2T>CSNV Pathogenic 503691 rs1556267388 X:103041657-103041657 X:103786728-103786728
4 PLP1 NM_000533.5(PLP1):c.166C>T (p.Gln56Ter)SNV Pathogenic 561088 rs1569427311 X:103040672-103040672 X:103785743-103785743
5 PLP1 NM_000533.5(PLP1):c.453+159G>ASNV Pathogenic 816705 X:103041814-103041814 X:103786885-103786885
6 PLP1 NM_000533.5(PLP1):c.453+164G>ASNV Pathogenic 816706 X:103041819-103041819 X:103786890-103786890
7 PLP1 NM_000533.5(PLP1):c.454-312C>GSNV Pathogenic 816707 X:103042415-103042415 X:103787486-103787486
8 PLP1 NM_000533.5(PLP1):c.646C>T (p.Pro216Ser)SNV Pathogenic 11073 rs132630278 X:103043389-103043389 X:103788460-103788460
9 PLP1 NM_000533.5(PLP1):c.44C>T (p.Pro15Leu)SNV Pathogenic 11075 rs11543022 X:103040550-103040550 X:103785621-103785621
10 PLP1 NM_000533.5(PLP1):c.467C>T (p.Thr156Ile)SNV Pathogenic 11076 rs132630280 X:103042740-103042740 X:103787811-103787811
11 PLP1 NM_000533.5(PLP1):c.655G>T (p.Val219Phe)SNV Pathogenic 11077 rs132630281 X:103043398-103043398 X:103788469-103788469
12 PLP1 PLP1, DELdeletion Pathogenic 11078
13 PLP1 NM_000533.5(PLP1):c.544A>C (p.Thr182Pro)SNV Pathogenic 11079 rs132630282 X:103042817-103042817 X:103787888-103787888
14 PLP1 NM_000533.5(PLP1):c.671T>C (p.Leu224Pro)SNV Pathogenic 11080 rs132630283 X:103043414-103043414 X:103788485-103788485
15 PLP1 NM_000533.5(PLP1):c.607G>C (p.Asp203His)SNV Pathogenic 11081 rs132630284 X:103042880-103042880 X:103787951-103787951
16 PLP1 NM_000533.5(PLP1):c.220G>A (p.Gly74Arg)SNV Pathogenic 11082 rs132630285 X:103041422-103041422 X:103786493-103786493
17 PLP1 NM_000533.5(PLP1):c.128C>T (p.Thr43Ile)SNV Pathogenic 11086 rs132630289 X:103040634-103040634 X:103785705-103785705
18 PLP1 PLP1, DUPduplication Pathogenic 11093
19 PLP1 NM_000533.5(PLP1):c.762+3G>TSNV Pathogenic 11094 rs1569428537 X:103044330-103044330 X:103789401-103789401
20 PLP1 NM_000533.5(PLP1):c.453+4A>GSNV Pathogenic 11096 rs1569427707 X:103041659-103041659 X:103786730-103786730
21 PLP1 NM_000533.5(PLP1):c.169G>T (p.Asp57Tyr)SNV Pathogenic 11099 rs132630296 X:103040675-103040675 X:103785746-103785746
22 PLP1 NM_000533.5(PLP1):c.1A>G (p.Met1Val)SNV Pathogenic 209183 rs797045064 X:103031924-103031924 X:103776996-103776996
23 PLP1 NM_000533.5(PLP1):c.295C>T (p.Gln99Ter)SNV Pathogenic 804067 X:103041497-103041497 X:103786568-103786568
24 PLP1 NM_000533.5(PLP1):c.551G>A (p.Cys184Tyr)SNV Likely pathogenic 804068 X:103042824-103042824 X:103787895-103787895
25 PLP1 NM_000533.5(PLP1):c.709T>G (p.Phe237Val)SNV Likely pathogenic 816628 X:103044274-103044274 X:103789345-103789345
26 PLP1 NM_000533.5(PLP1):c.487T>C (p.Trp163Arg)SNV Likely pathogenic 11074 rs132630279 X:103042760-103042760 X:103787831-103787831
27 PLP1 NM_000533.5(PLP1):c.104G>A (p.Cys35Tyr)SNV Likely pathogenic 626281 rs1569427275 X:103040610-103040610 X:103785681-103785681
28 GJC2 NM_020435.4(GJC2):c.591dup (p.His198fs)duplication Likely pathogenic 635342 1:228346048-228346049 1:228158347-228158348
29 PLP1 NM_000533.5(PLP1):c.658T>G (p.Cys220Gly)SNV Likely pathogenic 545437 rs1556270312 X:103043401-103043401 X:103788472-103788472
30 PLP1 NM_000533.5(PLP1):c.617T>G (p.Met206Arg)SNV Likely pathogenic 496683 rs1556269487 X:103042890-103042890 X:103787961-103787961
31 PLP1 NM_000533.5(PLP1):c.140T>C (p.Ile47Thr)SNV Likely pathogenic 405941 rs1060500909 X:103040646-103040646 X:103785717-103785717
32 PLP1 NM_000533.5(PLP1):c.518C>G (p.Pro173Arg)SNV Uncertain significance 547754 rs1556269029 X:103042791-103042791 X:103787862-103787862
33 PLP1 NM_000533.5(PLP1):c.41C>A (p.Ala14Asp)SNV Uncertain significance 561089 rs1569427243 X:103040547-103040547 X:103785618-103785618
34 PLP1 NM_000533.5(PLP1):c.677C>G (p.Ser226Cys)SNV Uncertain significance 561090 rs746949269 X:103043420-103043420 X:103788491-103788491
35 GJC2 NM_020435.4(GJC2):c.-20G>CSNV Uncertain significance 623303 rs1558116949 1:228337708-228337708 1:228150007-228150007

UniProtKB/Swiss-Prot genetic disease variations for Pelizaeus-Merzbacher Disease:

73 (show top 50) (show all 62)
# Symbol AA change Variation ID SNP ID
1 PLP1 p.Pro15Leu VAR_004546 rs11543022
2 PLP1 p.Thr43Ile VAR_004547 rs132630289
3 PLP1 p.Gly74Arg VAR_004548 rs132630285
4 PLP1 p.Thr156Ile VAR_004552 rs132630280
5 PLP1 p.Trp163Arg VAR_004553 rs132630279
6 PLP1 p.Val166Glu VAR_004554
7 PLP1 p.Thr182Pro VAR_004555 rs132630282
8 PLP1 p.Asp203His VAR_004557 rs132630284
9 PLP1 p.Pro216Ser VAR_004558 rs132630278
10 PLP1 p.Gly217Ser VAR_004559
11 PLP1 p.Val219Phe VAR_004560 rs132630281
12 PLP1 p.Gly221Cys VAR_004561 rs132630286
13 PLP1 p.Leu224Pro VAR_004562 rs132630283
14 PLP1 p.Ala249Pro VAR_004565
15 PLP1 p.Asp203Val VAR_007956
16 PLP1 p.Leu31Pro VAR_015014
17 PLP1 p.Phe32Leu VAR_015015
18 PLP1 p.Phe32Val VAR_015016
19 PLP1 p.Cys35Tyr VAR_015017
20 PLP1 p.Ala39Thr VAR_015018
21 PLP1 p.Leu46Pro VAR_015019
22 PLP1 p.Leu46Arg VAR_015020
23 PLP1 p.Phe51Ser VAR_015021
24 PLP1 p.Tyr60Cys VAR_015022
25 PLP1 p.Thr116Lys VAR_015023
26 PLP1 p.His148Tyr VAR_015025
27 PLP1 p.Lys151Asn VAR_015026
28 PLP1 p.Cys169Arg VAR_015028
29 PLP1 p.Val172Ala VAR_015030
30 PLP1 p.Tyr175Cys VAR_015031
31 PLP1 p.Trp181Cys VAR_015032
32 PLP1 p.Thr183Asn VAR_015033
33 PLP1 p.Asp203Glu VAR_015034
34 PLP1 p.Asp203Gly VAR_015035
35 PLP1 p.Asp203Asn VAR_015036 rs132630284
36 PLP1 p.Arg205Gly VAR_015037
37 PLP1 p.Tyr207Cys VAR_015038
38 PLP1 p.Val209Asp VAR_015039
39 PLP1 p.Leu210His VAR_015040
40 PLP1 p.Pro211Leu VAR_015041
41 PLP1 p.Trp212Arg VAR_015042
42 PLP1 p.Pro216Ala VAR_015043
43 PLP1 p.Cys220Tyr VAR_015044
44 PLP1 p.Cys228Tyr VAR_015047 rs398123466
45 PLP1 p.Gln234Pro VAR_015048
46 PLP1 p.Ala242Pro VAR_015049
47 PLP1 p.Gly246Glu VAR_015050
48 PLP1 p.Ala248Glu VAR_015051
49 PLP1 p.Ser253Phe VAR_015052
50 PLP1 p.Cys33Tyr VAR_046906 rs106479425

Copy number variations for Pelizaeus-Merzbacher Disease from CNVD:

7
# CNVD ID Chromosome Start End Type Gene Symbol CNVD Disease
1 257410 X 102500000 103600000 Microduplication Pelizaeus-Merzbacher disease
2 257431 X 102918094 102934203 Duplication PLP1 Pelizaeus-Merzbacher disease
3 266517 X 98200000 110500000 Deletion or duplication PLP1 Pelizaeus-Merzbacher disease
4 266518 X 98200000 110500000 Deletion or duplication PLP1 Pelizaeus-Merzbacher disease
5 266521 X 98200000 110500000 Microdeletion Pelizaeus-Merzbacher disease

Expression for Pelizaeus-Merzbacher Disease

Search GEO for disease gene expression data for Pelizaeus-Merzbacher Disease.

Pathways for Pelizaeus-Merzbacher Disease

Pathways related to Pelizaeus-Merzbacher Disease according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.34 PMP22 MPZ MBP
2 11.04 HUWE1 HMGA1 GAPDH
3 9.7 PLP1 MBP MAG

GO Terms for Pelizaeus-Merzbacher Disease

Cellular components related to Pelizaeus-Merzbacher Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 paranode region of axon GO:0033270 9.16 MAG GJC2
2 compact myelin GO:0043218 9.13 PMP22 MBP MAG
3 myelin sheath GO:0043209 9.02 PLP1 MPZ MBP MAG GJC2

Biological processes related to Pelizaeus-Merzbacher Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chemical synaptic transmission GO:0007268 9.67 PMP22 PLP1 MPZ MBP
2 response to toxic substance GO:0009636 9.61 MBP GJC2 ERCC6
3 isoprenoid biosynthetic process GO:0008299 9.46 PMVK MVK
4 substantia nigra development GO:0021762 9.43 PLP1 MBP ACTB
5 central nervous system myelination GO:0022010 9.4 PLP1 MAG
6 base-excision repair GO:0006284 9.33 HUWE1 HMGA1 ERCC6
7 axon ensheathment GO:0008366 9.32 PLP1 MBP
8 isopentenyl diphosphate biosynthetic process, mevalonate pathway GO:0019287 8.96 PMVK MVK
9 myelination GO:0042552 8.92 PMP22 PLP1 MPZ MBP

Molecular functions related to Pelizaeus-Merzbacher Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 structural constituent of myelin sheath GO:0019911 8.62 PLP1 MBP

Sources for Pelizaeus-Merzbacher Disease

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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