PMD
MCID: PLZ001
MIFTS: 65

Pelizaeus-Merzbacher Disease (PMD)

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

Aliases & Classifications for Pelizaeus-Merzbacher Disease

MalaCards integrated aliases for Pelizaeus-Merzbacher Disease:

Name: Pelizaeus-Merzbacher Disease 57 12 74 20 43 53 58 73 73 29 13 54 6 44 15 37 39 71
Pmd 57 12 20 43 58 73
Hld1 57 12 43 73
Pelizaeus-Merzbacher Brain Sclerosis 12 58 73
Sudanophilic Leukodystrophy, Paelizeus-Merzbacher Type 12 58
Cockayne-Pelizaeus-Merzbacher Disease 43 71
Pelizaeus Merzbacher Brain Sclerosis 12 20
Leukodystrophy, Hypomyelinating, 1 57 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 57
Diffuse Cerebral Sclerosis of Schilder 71
Pelizaeus-Merzbacher Disease Type Ii 58
Hypomyelinating Leukodystrophy, 1 43
Hypomyelinating Leukodystrophy 1 12
Brain Sclerosis Diffuse Familial 73
Leukodystrophy Hypomyelinating 1 73
Leukodystrophy, Sudanophilic 12
Pelizaeus Merzbacher Disease 20
Sudanophilic Leukodystrophy 43
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®:

57 (Updated 05-Mar-2021)
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

MedlinePlus Genetics : 43 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 and spastic paraplegia 2, x-linked, 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 Terpenoid backbone biosynthesis and Neural Crest Differentiation. The drugs Prednisolone acetate and Methylprednisolone hemisuccinate have been mentioned in the context of this disorder. Affiliated tissues include Spinal Cord and Brain, 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.

GARD : 20 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® : 57 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) (Updated 05-Mar-2021)

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 229)
# Related Disease Score Top Affiliating Genes
1 leukodystrophy 33.1 RARS1 PLP1 MPZ MAG GJC2
2 spastic paraplegia 2, x-linked 33.0 RAB9B PLP1 GJC2
3 pelizaeus-merzbacher-like disease 32.5 PLP1 GJC2
4 hypomyelinating leukodystrophy 32.3 SERPINA3 RARS1 PMVK PLP1 MYCBP2 HMGA1
5 demyelinating disease 31.3 SERPINA3 PMP22 PLP1 MPZ MBP MAG
6 spastic quadriplegia 31.2 RAB9B PLP1 ERCC6
7 charcot-marie-tooth disease 31.0 PMP22 PLP1 MPZ MBP MAG H2AC18
8 hypomyelinating leukoencephalopathy 31.0 PLP1 GJC2
9 peripheral nervous system disease 31.0 SERPINA3 PMP22 MPZ MBP MAG H2AC18
10 autosomal recessive disease 31.0 SERPINA3 MVK H2AC18 ERCC6
11 spastic paraplegia 75, autosomal recessive 31.0 PLP1 MAG GJC2
12 leukodystrophy, hypomyelinating, 9 31.0 RARS1 GJC2 ERCC6
13 neuropathy, hereditary, with liability to pressure palsies 30.9 PMP22 MPZ MAG
14 hereditary neuropathies 30.9 PMP22 PLP1 MPZ MBP MAG
15 charcot-marie-tooth disease, demyelinating, type 1a 30.9 PMP22 PLP1 MPZ MBP MAG
16 central nervous system disease 30.9 SERPINA3 PLP1 MBP H2AC18 ERCC6
17 tooth disease 30.9 SERPINA3 PMP22 PLP1 MPZ MBP H2AC18
18 x-linked recessive disease 30.8 SERPINA3 PLP1 H2AC18 GAPDH ERCC6 ACTB
19 distal arthrogryposis 30.8 SERPINA3 MAG H2AC18 GAPDH ADCY10 ACTB
20 polyneuropathy 30.3 PMP22 MPZ MBP MAG
21 disease of mental health 30.2 SERPINA3 RAB9B PLP1 MPZ MBP MAG
22 leukodystrophy, demyelinating, adult-onset, autosomal dominant 11.6
23 cerebral sclerosis similar to pelizaeus-merzbacher disease 11.5
24 autosomal dominant leukodystrophy with autonomic disease 11.4
25 leukodystrophy, hypomyelinating, 2 11.4
26 rh deficiency syndrome 11.4
27 pelizaeus-merzbacher disease, classic form 11.3
28 pelizaeus-merzbacher disease, transitional form 11.3
29 leukodystrophy, hypomyelinating, 3 11.3
30 pelizaeus-merzbacher disease in female carriers 11.3
31 microphthalmia, syndromic 9 11.2
32 rh-null, amorph type 11.0
33 pathologic nystagmus 11.0
34 pellucid marginal degeneration 10.9
35 paraplegia 10.8
36 plp1 disorders 10.8
37 spasticity 10.8
38 hypotonia 10.8
39 ataxia and polyneuropathy, adult-onset 10.7
40 cerebral palsy 10.6
41 tremor 10.6
42 pseudohypoparathyroidism, type ii 10.5 PDE3B ADCY10
43 central pontine myelinolysis 10.5 MBP MAG GJC2
44 leukodystrophy, hypomyelinating, 5 10.5 PLP1 GJC2 ERCC6
45 charcot-marie-tooth disease type x 10.5 PMP22 MPZ GJC2
46 allergic encephalomyelitis 10.5 PLP1 MBP
47 charcot-marie-tooth disease, x-linked dominant, 1 10.5 PMP22 MPZ GJC2
48 mononeuropathy 10.5 PMP22 MPZ MAG
49 chromosome 18q deletion syndrome 10.5 MBP GJC2 ERCC6
50 polyradiculoneuropathy 10.5 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 83)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 nystagmus 58 31 obligate (100%) Very frequent (99-80%),Excluded (0%),Very frequent (99-80%) HP:0000639
2 psychomotor deterioration 31 obligate (100%) HP:0002361
3 spasticity 58 31 hallmark (90%) Very frequent (99-80%) HP:0001257
4 scoliosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0002650
5 ataxia 58 31 hallmark (90%) Very frequent (99-80%),Frequent (79-30%),Frequent (79-30%) HP:0001251
6 gait disturbance 58 31 hallmark (90%) Very frequent (99-80%) HP:0001288
7 kyphosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0002808
8 developmental regression 58 31 hallmark (90%) Very frequent (99-80%) HP:0002376
9 behavioral abnormality 58 31 hallmark (90%) Very frequent (99-80%) HP:0000708
10 joint stiffness 58 31 hallmark (90%) Very frequent (99-80%) HP:0001387
11 visual impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0000505
12 optic atrophy 58 31 frequent (33%) Very frequent (99-80%),Occasional (29-5%) HP:0000648
13 intellectual disability, severe 58 31 hallmark (90%) Very frequent (99-80%) HP:0010864
14 failure to thrive in infancy 58 31 hallmark (90%) Very frequent (99-80%) HP:0001531
15 cerebral cortical atrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0002120
16 cachexia 58 31 hallmark (90%) Very frequent (99-80%) HP:0004326
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 progressive spastic quadriplegia 58 31 hallmark (90%) Occasional (29-5%) HP:0002478
20 demyelinating peripheral neuropathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0007108
21 lower limb spasticity 58 31 hallmark (90%) Very frequent (99-80%) HP:0002061
22 cerebral hypomyelination 58 31 hallmark (90%) Very frequent (99-80%) HP:0006808
23 cns hypomyelination 58 31 hallmark (90%) Very frequent (99-80%) HP:0003429
24 gliosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0002171
25 lower limb amyotrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0007210
26 peripheral demyelination 58 31 hallmark (90%) Very frequent (99-80%) HP:0011096
27 abnormal pyramidal sign 31 hallmark (90%) HP:0007256
28 global developmental delay 31 hallmark (90%) HP:0001263
29 hypotonia 31 hallmark (90%) HP:0001252
30 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
31 failure to thrive 58 31 frequent (33%) Occasional (29-5%) HP:0001508
32 neurological speech impairment 58 31 frequent (33%) Frequent (79-30%) HP:0002167
33 dysarthria 58 31 frequent (33%) Frequent (79-30%) HP:0001260
34 respiratory insufficiency 58 31 frequent (33%) Frequent (79-30%) HP:0002093
35 bowel incontinence 58 31 frequent (33%) Frequent (79-30%) HP:0002607
36 hearing impairment 58 31 occasional (7.5%) Frequent (79-30%) HP:0000365
37 recurrent respiratory infections 58 31 frequent (33%) Frequent (79-30%) HP:0002205
38 microcephaly 58 31 frequent (33%) Frequent (79-30%) HP:0000252
39 short stature 58 31 frequent (33%) Frequent (79-30%),Occasional (29-5%) HP:0004322
40 abnormality of visual evoked potentials 58 31 frequent (33%) Frequent (79-30%) HP:0000649
41 decreased nerve conduction velocity 58 31 frequent (33%) Frequent (79-30%) HP:0000762
42 absent speech 58 31 frequent (33%) Frequent (79-30%) HP:0001344
43 arteriovenous malformation 58 31 frequent (33%) Frequent (79-30%) HP:0100026
44 abnormality of the urinary system 58 31 frequent (33%) Frequent (79-30%) HP:0000079
45 poor head control 58 31 frequent (33%) Frequent (79-30%) HP:0002421
46 choreoathetosis 58 31 frequent (33%) Frequent (79-30%) HP:0001266
47 progressive spastic paraplegia 58 31 frequent (33%) Frequent (79-30%) HP:0007020
48 difficulty walking 58 31 occasional (7.5%) Frequent (79-30%),Occasional (29-5%) HP:0002355
49 inability to walk 58 31 frequent (33%) Occasional (29-5%),Frequent (79-30%) HP:0002540
50 laryngeal stridor 58 31 frequent (33%) Frequent (79-30%) HP:0006511

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
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 (Updated 05-Mar-2021)

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 13)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00221-A-1 10.05 PMVK
2 Decreased viability GR00221-A-2 10.05 PMVK
3 Decreased viability GR00221-A-4 10.05 PMVK
4 Decreased viability GR00240-S-1 10.05 ADCY10
5 Decreased viability GR00249-S 10.05 ADCY10 GAPDH HMGA1 MPZ PDE3B PMVK
6 Decreased viability GR00342-S-1 10.05 PMVK
7 Decreased viability GR00342-S-2 10.05 PMVK
8 Decreased viability GR00342-S-3 10.05 PMVK
9 Decreased viability GR00381-A-1 10.05 ACTB MPZ
10 Decreased viability GR00381-A-3 10.05 MPZ
11 Decreased viability GR00386-A-1 10.05 ERCC6 MPZ RAB9B
12 Decreased viability GR00402-S-2 10.05 ACTB MBP MPZ RAB9B RARS1
13 Reduced mammosphere formation GR00396-S 9.17 ACTB GAPDH MAG MVD MVK PLP1

MGI Mouse Phenotypes related to Pelizaeus-Merzbacher Disease:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.73 ACTB ERCC6 GJC2 MAG MBP MPZ
2 hearing/vestibular/ear MP:0005377 9.1 ACTB ERCC6 MAG MBP PLP1 PMP22

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 acetate Approved, Vet_approved Phase 3 52-21-1
2
Methylprednisolone hemisuccinate Approved Phase 3 2921-57-5
3
Prednisolone phosphate Approved, Vet_approved Phase 3 302-25-0
4
Methylprednisolone Approved, Vet_approved Phase 3 83-43-2 6741
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 Efficacy and Safety Study of Vatiquinone for the Treatment of Mitochondrial Disease Subjects With Refractory Epilepsy Recruiting NCT04378075 Phase 2, Phase 3 Vatiquinone
3 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
4 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
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, Spinal Cord, Eye, Cerebellum, Bone Marrow, 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 Spinal Cord Spinal Cord White Matter Myelinating Oligodendrocyte Cells Affected by disease
2 Brain Forebrain White Matter Myelinating Oligodendrocyte Cells Affected by disease

Publications for Pelizaeus-Merzbacher Disease

Articles related to Pelizaeus-Merzbacher Disease:

(show top 50) (show all 555)
# Title Authors PMID Year
1
Complete deletion of the proteolipid protein gene (PLP) in a family with X-linked Pelizaeus-Merzbacher disease. 61 57 6 54
1720927 1991
2
Pelizaeus-Merzbacher disease: identification of Xq22 proteolipid-protein duplications and characterization of breakpoints by interphase FISH. 61 6 57
9634530 1998
3
Pelizaeus-Merzbacher disease: tight linkage to proteolipid protein gene exon variant. 61 57 6
2480601 1989
4
Mutation of the proteolipid protein gene PLP in a human X chromosome-linked myelin disorder. 61 57 6
2479017 1989
5
Pelizaeus-Merzbacher disease: an X-linked neurologic disorder of myelin metabolism with a novel mutation in the gene encoding proteolipid protein. 57 6 61
2773936 1989
6
Defective biosynthesis of proteolipid protein in Pelizaeus-Merzbacher disease. 61 57 6
3827224 1987
7
Arena syndrome is caused by a missense mutation in PLP1. 57 6
19396823 2009
8
Spastic paraplegia with iron deposits in the basal ganglia: a new X-linked mental retardation syndrome. 57 6
1605230 1992
9
Genotype-phenotype correlation in five Pelizaeus-Merzbacher disease patients with PLP1 gene duplications. 57 54 61
18190592 2008
10
Pelizaeus-Merzbacher syndrome: neurocognitive function in a family with carrier manifestations. 54 61 57
17568416 2007
11
Heterogeneous duplications in patients with Pelizaeus-Merzbacher disease suggest a mechanism of coupled homologous and nonhomologous recombination. 61 6 54
16380909 2005
12
Quantitative proton MRS of Pelizaeus-Merzbacher disease: evidence of dys- and hypomyelination. 54 61 57
16157902 2005
13
Complex chromosomal rearrangement and associated counseling issues in a family with Pelizaeus-Merzbacher disease. 54 6 61
12605435 2003
14
Genomic rearrangements resulting in PLP1 deletion occur by nonhomologous end joining and cause different dysmyelinating phenotypes in males and females. 6 61 54
12297985 2002
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. 61 54 57
10417279 1999
16
Prenatal diagnosis by FISH in a family with Pelizaeus-Merzbacher disease caused by duplication of PLP gene. 57 61 54
10210128 1999
17
Duplication of the proteolipid protein gene is the major cause of Pelizaeus-Merzbacher disease. 6 54 61
9633722 1998
18
A cellular mechanism governing the severity of Pelizaeus-Merzbacher disease. 54 61 57
8696336 1996
19
A duplicated PLP gene causing Pelizaeus-Merzbacher disease detected by comparative multiplex PCR. 57 54 61
8659540 1996
20
Overexpression of DM20 messenger RNA in two brothers with Pelizaeus-Merzbacher disease. 61 54 6
7574457 1995
21
Dominant-negative action of the jimpy mutation in mice complemented with an autosomal transgene for myelin proteolipid protein. 57 54 61
7538670 1995
22
Girl with signs of Pelizaeus-Merzbacher disease heterozygous for a mutation in exon 2 of the proteolipid protein gene. 61 54 57
7539211 1995
23
Premature arrest of myelin formation in transgenic mice with increased proteolipid protein gene dosage. 57 54 61
7512350 1994
24
Pelizaeus-Merzbacher disease: detection of mutations Thr181----Pro and Leu223----Pro in the proteolipid protein gene, and prenatal diagnosis. 6 54 61
1384324 1992
25
Uncoupling of hypomyelination and glial cell death by a mutation in the proteolipid protein gene. 57 61 54
1380672 1992
26
A new mutation in the proteolipid protein (PLP) gene in a German family with Pelizaeus-Merzbacher disease. 54 6 61
1707231 1991
27
Distinct patterns of complex rearrangements and a mutational signature of microhomeology are frequently observed in PLP1 copy number gain structural variants. 57 61
31818324 2019
28
Progesterone antagonist therapy in a Pelizaeus-Merzbacher mouse model. 61 57
24680886 2014
29
Depletion of molecular chaperones from the endoplasmic reticulum and fragmentation of the Golgi apparatus associated with pathogenesis in Pelizaeus-Merzbacher disease. 61 57
23344956 2013
30
Evidence for disease penetrance relating to CNV size: Pelizaeus-Merzbacher disease and manifesting carriers with a familial 11 Mb duplication at Xq22. 57 61
21623770 2012
31
The burden of inherited leukodystrophies in children. 61 57
20660364 2010
32
Clinical neurophysiology in GJA12-related hypomyelination vs Pelizaeus-Merzbacher disease. 57 61
20513814 2010
33
Quantifying the carrier female phenotype in Pelizaeus-Merzbacher disease. 57 61
16778599 2006
34
Primary progressive multiple sclerosis as a phenotype of a PLP1 gene mutation. 61 57
16130097 2005
35
PLP1-related inherited dysmyelinating disorders: Pelizaeus-Merzbacher disease and spastic paraplegia type 2. 57 61
15627202 2005
36
The unfolded protein response modulates disease severity in Pelizaeus-Merzbacher disease. 61 57
12441049 2002
37
Compensating for central nervous system dysmyelination: females with a proteolipid protein gene duplication and sustained clinical improvement. 57 61
11761472 2001
38
Genotype-phenotype correlation in inherited brain myelination defects due to proteolipid protein gene mutations. Clinical European Network on Brain Dysmyelinating Disease. 57 61
11093273 2000
39
Mutations in noncoding regions of the proteolipid protein gene in Pelizaeus-Merzbacher disease. 6 61
11071483 2000
40
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
41
Pelizaeus-Merzbacher disease presenting as spinal muscular atrophy: clinical and molecular studies. 57 61
7998780 1994
42
Genetic homogeneity of Pelizaeus-Merzbacher disease: tight linkage to the proteolipoprotein locus in 16 affected families. PMD Clinical Group. 61 57
7915877 1994
43
Genetics of Pelizaeus-Merzbacher disease. 61 57
7530633 1993
44
Molecular diagnostics for myelin proteolipid protein gene mutations in Pelizaeus-Merzbacher disease. 61 6
1376966 1992
45
Pelizaeus-Merzbacher disease: clinical and DNA-linkage study of an extended family. 57 61
1789292 1991
46
Pelizaeus-Merzbacher disease: a valine to phenylalanine point mutation in a putative extracellular loop of myelin proteolipid. 6 61
1715570 1991
47
Carrier detection and prenatal diagnosis of Pelizaeus-Merzbacher disease using a combination of anonymous DNA polymorphisms and the proteolipid protein (PLP) gene cDNA. 57 61
1676565 1991
48
The otolaryngologic manifestations of Pelizaeus-Merzbacher disease. 61 57
2328119 1990
49
Pelizaeus-Merzbacher disease: identification of heterozygotes with magnetic resonance imaging? 57 61
3198119 1988
50
Comparative immunocytochemistry of Pelizaeus-Merzbacher disease, the jimpy mouse, and the myelin-deficient rat. 57 61
2454299 1988

Variations for Pelizaeus-Merzbacher Disease

ClinVar genetic disease variations for Pelizaeus-Merzbacher Disease:

6 (show all 39)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 RAB9B NM_000533.5(PLP1):c.44C>T (p.Pro15Leu) SNV Pathogenic 11075 rs11543022 X:103040550-103040550 X:103785621-103785621
2 RAB9B NM_000533.5(PLP1):c.467C>T (p.Thr156Ile) SNV Pathogenic 11076 rs132630280 X:103042740-103042740 X:103787811-103787811
3 RAB9B NM_000533.5(PLP1):c.655G>T (p.Val219Phe) SNV Pathogenic 11077 rs132630281 X:103043398-103043398 X:103788469-103788469
4 PLP1 PLP1, DEL Deletion Pathogenic 11078
5 RAB9B NM_000533.5(PLP1):c.544A>C (p.Thr182Pro) SNV Pathogenic 11079 rs132630282 X:103042817-103042817 X:103787888-103787888
6 RAB9B NM_000533.5(PLP1):c.671T>C (p.Leu224Pro) SNV Pathogenic 11080 rs132630283 X:103043414-103043414 X:103788485-103788485
7 RAB9B NM_000533.5(PLP1):c.607G>C (p.Asp203His) SNV Pathogenic 11081 rs132630284 X:103042880-103042880 X:103787951-103787951
8 RAB9B NM_000533.5(PLP1):c.220G>A (p.Gly74Arg) SNV Pathogenic 11082 rs132630285 X:103041422-103041422 X:103786493-103786493
9 RAB9B NM_000533.5(PLP1):c.128C>T (p.Thr43Ile) SNV Pathogenic 11086 rs132630289 X:103040634-103040634 X:103785705-103785705
10 PLP1 PLP1, DUP Duplication Pathogenic 11093
11 RAB9B NM_000533.5(PLP1):c.762+3G>T SNV Pathogenic 11094 rs1569428537 X:103044330-103044330 X:103789401-103789401
12 RAB9B NM_000533.5(PLP1):c.453+2T>C SNV Pathogenic 503691 rs1556267388 X:103041657-103041657 X:103786728-103786728
13 RAB9B NM_000533.5(PLP1):c.453+4A>G SNV Pathogenic 11096 rs1569427707 X:103041659-103041659 X:103786730-103786730
14 RAB9B NM_000533.5(PLP1):c.169G>T (p.Asp57Tyr) SNV Pathogenic 11099 rs132630296 X:103040675-103040675 X:103785746-103785746
15 RAB9B NM_000533.5(PLP1):c.1A>G (p.Met1Val) SNV Pathogenic 209183 rs797045064 X:103031924-103031924 X:103776996-103776996
16 RAB9B NM_000533.5(PLP1):c.175G>T (p.Glu59Ter) SNV Pathogenic 397513 rs1060499653 X:103040681-103040681 X:103785752-103785752
17 RAB9B NM_000533.5(PLP1):c.384_393del (p.Gln129fs) Deletion Pathogenic 431701 rs1556267215 X:103041586-103041595 X:103786657-103786666
18 RAB9B NM_000533.5(PLP1):c.166C>T (p.Gln56Ter) SNV Pathogenic 561088 rs1569427311 X:103040672-103040672 X:103785743-103785743
19 RAB9B NM_000533.5(PLP1):c.453+159G>A SNV Pathogenic 816705 rs1602383261 X:103041814-103041814 X:103786885-103786885
20 RAB9B NM_000533.5(PLP1):c.453+164G>A SNV Pathogenic 816706 rs1602383268 X:103041819-103041819 X:103786890-103786890
21 RAB9B NM_000533.5(PLP1):c.454-312C>G SNV Pathogenic 816707 rs1602383723 X:103042415-103042415 X:103787486-103787486
22 RAB9B NM_000533.5(PLP1):c.173A>G (p.Tyr58Cys) SNV Pathogenic 930478 X:103040679-103040679 X:103785750-103785750
23 RAB9B NM_000533.5(PLP1):c.295C>T (p.Gln99Ter) SNV Pathogenic 804067 rs1602382829 X:103041497-103041497 X:103786568-103786568
24 RAB9B NM_000533.5(PLP1):c.646C>T (p.Pro216Ser) SNV Pathogenic 11073 rs132630278 X:103043389-103043389 X:103788460-103788460
25 RAB9B NM_000533.5(PLP1):c.487T>C (p.Trp163Arg) SNV Pathogenic 11074 rs132630279 X:103042760-103042760 X:103787831-103787831
26 RAB9B NM_000533.5(PLP1):c.551G>A (p.Cys184Tyr) SNV Likely pathogenic 804068 rs1602384238 X:103042824-103042824 X:103787895-103787895
27 RAB9B NM_000533.5(PLP1):c.709T>G (p.Phe237Val) SNV Likely pathogenic 816628 rs1602385663 X:103044274-103044274 X:103789345-103789345
28 RAB9B NM_000533.5(PLP1):c.743C>A (p.Ala248Glu) SNV Likely pathogenic 931338 X:103044308-103044308 X:103789379-103789379
29 RAB9B NM_000533.5(PLP1):c.658T>G (p.Cys220Gly) SNV Likely pathogenic 545437 rs1556270312 X:103043401-103043401 X:103788472-103788472
30 RAB9B NM_000533.5(PLP1):c.140T>C (p.Ile47Thr) SNV Likely pathogenic 405941 rs1060500909 X:103040646-103040646 X:103785717-103785717
31 RAB9B NM_000533.5(PLP1):c.104G>A (p.Cys35Tyr) SNV Likely pathogenic 626281 rs1569427275 X:103040610-103040610 X:103785681-103785681
32 GJC2 NM_020435.4(GJC2):c.591dup (p.His198fs) Duplication Likely pathogenic 635342 rs1455411788 1:228346048-228346049 1:228158347-228158348
33 RAB9B NM_000533.5(PLP1):c.617T>G (p.Met206Arg) SNV Likely pathogenic 496683 rs1556269487 X:103042890-103042890 X:103787961-103787961
34 GJC2 NM_020435.4(GJC2):c.-20G>C SNV Uncertain significance 623303 rs1558116949 1:228337708-228337708 1:228150007-228150007
35 RAB9B NM_000533.5(PLP1):c.518C>G (p.Pro173Arg) SNV Uncertain significance 547754 rs1556269029 X:103042791-103042791 X:103787862-103787862
36 RAB9B NM_000533.5(PLP1):c.41C>A (p.Ala14Asp) SNV Uncertain significance 561089 rs1569427243 X:103040547-103040547 X:103785618-103785618
37 RAB9B NM_000533.5(PLP1):c.677C>G (p.Ser226Cys) SNV Uncertain significance 561090 rs746949269 X:103043420-103043420 X:103788491-103788491
38 RAB9B NM_000533.5(PLP1):c.49G>A (p.Ala17Thr) SNV Uncertain significance 211916 rs797045890 X:103040555-103040555 X:103785626-103785626
39 RAB9B NM_000533.5(PLP1):c.-31C>T SNV Benign 220658 rs2233695 X:103031893-103031893 X:103776965-103776965

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

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 myelin sheath GO:0043209 9.02 PLP1 MPZ MBP MAG GJC2
3 compact myelin GO:0043218 8.96 MBP MAG

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

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 chemical synaptic transmission GO:0007268 9.8 PMP22 PLP1 MPZ MBP
2 cholesterol metabolic process GO:0008203 9.71 PMVK MVK MVD
3 response to toxic substance GO:0009636 9.69 MBP GJC2 ERCC6
4 steroid biosynthetic process GO:0006694 9.65 PMVK MVK MVD
5 myelination GO:0042552 9.61 PLP1 MPZ MBP
6 cholesterol biosynthetic process GO:0006695 9.58 PMVK MVK MVD
7 regulation of cholesterol biosynthetic process GO:0045540 9.54 PMVK MVK MVD
8 central nervous system myelination GO:0022010 9.52 PLP1 MAG
9 sterol biosynthetic process GO:0016126 9.5 PMVK MVK MVD
10 axon ensheathment GO:0008366 9.46 PLP1 MBP
11 isoprenoid biosynthetic process GO:0008299 9.33 PMVK MVK MVD
12 positive regulation of calcium ion transmembrane transport GO:1904427 9.26 PLP1 GJC2
13 substantia nigra development GO:0021762 9.26 PLP1 MBP MAG ACTB
14 isopentenyl diphosphate biosynthetic process, mevalonate pathway GO:0019287 8.8 PMVK MVK MVD

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

# Name GO ID Score Top Affiliating Genes
1 ATP binding GO:0005524 9.7 RARS1 PMVK MVK MVD ERCC6 ADCY10
2 nucleotide binding GO:0000166 9.28 RARS1 RAB9B PMVK MVK MVD GAPDH
3 structural constituent of myelin sheath GO:0019911 8.96 PLP1 MBP

Sources for Pelizaeus-Merzbacher Disease

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....