MCID: LKD010
MIFTS: 45

Leukodystrophy, Hypomyelinating, 2

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

Aliases & Classifications for Leukodystrophy, Hypomyelinating, 2

MalaCards integrated aliases for Leukodystrophy, Hypomyelinating, 2:

Name: Leukodystrophy, Hypomyelinating, 2 57 75 29 13 6 73
Pmld1 57 12 24 25 59 75
Hld2 57 12 24 25 75
Hypomyelinating Leukodystrophy 2 12 24 25 15
Pelizaeus-Merzbacher-Like Disease Due to Gjc2 Mutation 12 59
Pelizaeus-Merzbacher-Like Disease Type 1 25 75
Pelizaeus-Merzbacher-Like Disease 1 12 24
Pelizaeus-Merzbacher-Like Disease Autosomal Recessive Type 1 75
Pelizaeus-Merzbacher-Like Disease, 1; Pmld1 57
Leukodystrophy, Hypomyelinating, Type 2 ) 40
Pmld - Pelizaeus Merzbacher Like Disease 25
Pelizaeus-Merzbacher-Like Disease, 1 57
Pelizaeus-Merzbacher-Like Disease 25
Pelizaeus Merzbacher Like Disease 25
Pmldar1 75

Characteristics:

Orphanet epidemiological data:

59
pelizaeus-merzbacher-like disease due to gjc2 mutation
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
most children become wheelchair-bound
similar disorder to x-linked pelizaeus-merzbacher disease (pmd, )


HPO:

32
leukodystrophy, hypomyelinating, 2:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Rare neurological diseases


Summaries for Leukodystrophy, Hypomyelinating, 2

Genetics Home Reference : 25 Pelizaeus-Merzbacher-like disease type 1 is an inherited condition involving the brain and spinal cord (central nervous system). This disease is one of a group of genetic disorders called leukodystrophies. Leukodystrophies are 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-like disease type 1 involves hypomyelination, which means that the nervous system has a reduced ability to form myelin. The signs and symptoms of this condition are very similar to another leukodystrophy called Pelizaeus-Merzbacher disease, but the two disorders have different genetic causes.

MalaCards based summary : Leukodystrophy, Hypomyelinating, 2, also known as pmld1, is related to pelizaeus-merzbacher-like disease and pelizaeus-merzbacher disease, and has symptoms including ataxia, muscle rigidity and seizures. An important gene associated with Leukodystrophy, Hypomyelinating, 2 is GJC2 (Gap Junction Protein Gamma 2), and among its related pathways/superpathways are Neural Crest Differentiation and Glial Cell Differentiation. Affiliated tissues include brain and spinal cord, and related phenotypes are seizures and ataxia

UniProtKB/Swiss-Prot : 75 Leukodystrophy, hypomyelinating, 2: An autosomal recessive hypomyelinating leukodystrophy with symptoms of Pelizaeus-Merzbacher disease. Clinically characterized by nystagmus, impaired motor development, ataxia, choreoathetotic movements, dysarthria, and progressive spasticity.

Disease Ontology : 12 A hypomyelinating leukodystrophy characterized by autosomal recessive inheritance of nystagmus, impaired motor development, ataxia, choreoathetotic movements, dysarthria, and progressive spasticity that has material basis in homozygous or compound heterozygous mutation in the GJC2 gene on chromosome 1q42.

Description from OMIM: 608804
GeneReviews: NBK470716

Related Diseases for Leukodystrophy, Hypomyelinating, 2

Diseases in the Hypomyelinating Leukodystrophy family:

Leukodystrophy, Hypomyelinating, 3 Leukodystrophy, Hypomyelinating, 2
Leukodystrophy, Hypomyelinating, 5 Leukodystrophy, Hypomyelinating, 4
Leukodystrophy, Hypomyelinating, 6 Leukodystrophy, Hypomyelinating, 9
Leukodystrophy, Hypomyelinating, 10 Leukodystrophy, Hypomyelinating, 11
Leukodystrophy, Hypomyelinating, 12 Leukodystrophy, Hypomyelinating, 13
Leukodystrophy, Hypomyelinating, 14 Leukodystrophy, Hypomyelinating, 15
Leukodystrophy, Hypomyelinating, 16 Leukodystrophy, Hypomyelinating, 17

Diseases related to Leukodystrophy, Hypomyelinating, 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 40)
# Related Disease Score Top Affiliating Genes
1 pelizaeus-merzbacher-like disease 30.9 GJB1 GJC2 PLP1 SNAP29
2 pelizaeus-merzbacher disease 30.6 GJC2 MBP PLP1
3 cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome 10.8 PI4KA SNAP29
4 charcot-marie-tooth disease, x-linked dominant, 1 10.7 GJB1 GJC2
5 leukodystrophy, hypomyelinating, 4 10.7 GJC2 PLP1
6 hypomyelinating leukoencephalopathy 10.7 GJC2 PLP1
7 spastic paraplegia 2, x-linked 10.7 GJC2 PLP1
8 neurodegeneration with brain iron accumulation 2b 10.6 FA2H PANK2
9 hypomyelinating leukodystrophy 10.5 GJB1 GJC2 PLP1
10 cerebral degeneration 10.4 FA2H GJC2 PLP1
11 allergic encephalomyelitis 10.4 MBP PLP1
12 leukodystrophy 10.4 FA2H GJC2 PLP1
13 neurodegeneration with brain iron accumulation 3 10.3 FA2H JPH3 PANK2
14 niemann-pick disease, type a 10.3 MBP PLP1
15 neurodegeneration with brain iron accumulation 6 10.3 PANK2 VPS13A
16 oromandibular dystonia 10.3 GCH1 TOR1A
17 segmental dystonia 10.3 GCH1 TOR1A
18 extratemporal epilepsy 10.3 PLP1 TOR1A
19 early-onset generalized dystonia 10.2 GCH1 TOR1A
20 neurodegeneration with brain iron accumulation 10.2 FA2H PANK2 VPS13A
21 focal hand dystonia 10.2 PANK2 TOR1A
22 choreoacanthocytosis 10.2 HCCS JPH3 VPS13A
23 hereditary neuropathies 10.1 GJB1 MBP PLP1
24 blepharospasm 10.1 GCH1 TOR1A
25 thiamine metabolism dysfunction syndrome 2 10.1 GCH1 TOR1A
26 cranio-facial dystonia 10.1 GCH1 GJC2 TOR1A
27 lymphedema, hereditary, ii 10.1 GCH1 GJC2 TOR1A
28 cervical dystonia 10.1 GCH1 TOR1A
29 huntington disease-like 2 10.1 HTT JPH3
30 dystonia 1, torsion, autosomal dominant 10.1 GCH1 TOR1A
31 neurodegeneration with brain iron accumulation 1 10.0 FA2H JPH3 PANK2 VPS13A
32 hallermann-streiff syndrome 10.0 GJB1 GJC2
33 hereditary spastic paraplegia 10.0 FA2H GJC2 PLP1
34 hemidystonia 10.0 GCH1 TOR1A
35 dystonia 12 10.0 GCH1 PANK2 TOR1A
36 choreatic disease 9.8 HTT JPH3 VPS13A
37 dystonia, dopa-responsive 9.8 GCH1 TOR1A
38 trehalase deficiency 9.7 FA2H GJB1 GJC2 PANK2 PLP1
39 dystonia 9.5 FA2H GCH1 PANK2 TOR1A
40 movement disease 9.0 GCH1 HTT PANK2 TOR1A

Graphical network of the top 20 diseases related to Leukodystrophy, Hypomyelinating, 2:



Diseases related to Leukodystrophy, Hypomyelinating, 2

Symptoms & Phenotypes for Leukodystrophy, Hypomyelinating, 2

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
seizures
ataxia
dysarthria
dystonia
rigidity
more
Neurologic Peripheral Nervous System:
demyelinating motor neuropathy
axonal sensory neuropathy
decreased motor nerve conduction velocities (ncv)
peripheral neuropathy, mild (less common)

Head And Neck Head:
head titubation

Head And Neck Eyes:
optic atrophy
myopia
rotary nystagmus

Head And Neck Face:
facial weakness


Clinical features from OMIM:

608804

Human phenotypes related to Leukodystrophy, Hypomyelinating, 2:

32 (show all 26)
# Description HPO Frequency HPO Source Accession
1 seizures 32 HP:0001250
2 ataxia 32 HP:0001251
3 dysarthria 32 HP:0001260
4 facial palsy 32 HP:0010628
5 global developmental delay 32 HP:0001263
6 optic atrophy 32 HP:0000648
7 cognitive impairment 32 HP:0100543
8 myopia 32 HP:0000545
9 babinski sign 32 HP:0003487
10 intention tremor 32 HP:0002080
11 sensory axonal neuropathy 32 HP:0003390
12 dystonia 32 HP:0001332
13 decreased motor nerve conduction velocity 32 HP:0003431
14 rigidity 32 HP:0002063
15 choreoathetosis 32 HP:0001266
16 progressive spasticity 32 HP:0002191
17 motor delay 32 HP:0001270
18 cerebral atrophy 32 HP:0002059
19 leukodystrophy 32 HP:0002415
20 spastic paraparesis 32 HP:0002313
21 poor speech 32 HP:0002465
22 muscular hypotonia of the trunk 32 HP:0008936
23 demyelinating motor neuropathy 32 HP:0007220
24 cerebral hypomyelination 32 HP:0006808
25 head titubation 32 HP:0002599
26 rotary nystagmus 32 HP:0001583

UMLS symptoms related to Leukodystrophy, Hypomyelinating, 2:


ataxia, muscle rigidity, seizures, paraparesis, spastic, action tremor, facial paresis, head titubation

GenomeRNAi Phenotypes related to Leukodystrophy, Hypomyelinating, 2 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Moderately decreased NFAT1-GFP nuclear translocation GR00359-A 9.02 HTT MBP NRAS PI4KA VPS13A

MGI Mouse Phenotypes related to Leukodystrophy, Hypomyelinating, 2:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.32 PLP1 SNAP29 TOR1A VPS13A DLL1 FA2H
2 growth/size/body region MP:0005378 10.21 DLL1 GJB1 HCCS HTT JPH3 MBP
3 cellular MP:0005384 10.2 DLL1 GJB1 GJC2 HCCS SNAP29 TOR1A
4 homeostasis/metabolism MP:0005376 10.15 DLL1 FA2H GCH1 GJB1 HCCS HTT
5 hematopoietic system MP:0005397 10.1 PANK2 PI4KA PLP1 VPS13A DLL1 GJB1
6 mortality/aging MP:0010768 10.1 DLL1 GCH1 GJB1 GJC2 HCCS HTT
7 immune system MP:0005387 10.02 DLL1 GJB1 GJC2 HTT MBP NRAS
8 nervous system MP:0003631 9.93 TOR1A VPS13A DLL1 FA2H GCH1 GJB1
9 normal MP:0002873 9.56 DLL1 GJC2 HCCS HTT MBP NRAS
10 vision/eye MP:0005391 9.23 FA2H GJB1 GJC2 MBP NRAS PANK2

Drugs & Therapeutics for Leukodystrophy, Hypomyelinating, 2

Search Clinical Trials , NIH Clinical Center for Leukodystrophy, Hypomyelinating, 2

Genetic Tests for Leukodystrophy, Hypomyelinating, 2

Genetic tests related to Leukodystrophy, Hypomyelinating, 2:

# Genetic test Affiliating Genes
1 Leukodystrophy, Hypomyelinating, 2 29 GJC2

Anatomical Context for Leukodystrophy, Hypomyelinating, 2

MalaCards organs/tissues related to Leukodystrophy, Hypomyelinating, 2:

41
Brain, Spinal Cord

Publications for Leukodystrophy, Hypomyelinating, 2

Articles related to Leukodystrophy, Hypomyelinating, 2:

# Title Authors Year
1
Pelizaeus-Merzbacher disease, Pelizaeus-Merzbacher-like disease 1, and related hypomyelinating disorders. ( 22422208 )
2012
2
Pelizaeus-Merzbacher-Like Disease 1 ( 29276893 )
1993

Variations for Leukodystrophy, Hypomyelinating, 2

UniProtKB/Swiss-Prot genetic disease variations for Leukodystrophy, Hypomyelinating, 2:

75
# Symbol AA change Variation ID SNP ID
1 GJC2 p.Pro90Ser VAR_023754 rs74315312
2 GJC2 p.Tyr272Asp VAR_023755 rs74315314
3 GJC2 p.Met286Thr VAR_023756 rs74315311

ClinVar genetic disease variations for Leukodystrophy, Hypomyelinating, 2:

6
(show all 28)
# Gene Variation Type Significance SNP ID Assembly Location
1 GJC2 NM_020435.3(GJC2): c.857T> C (p.Met286Thr) single nucleotide variant Pathogenic rs74315311 GRCh37 Chromosome 1, 228346316: 228346316
2 GJC2 NM_020435.3(GJC2): c.857T> C (p.Met286Thr) single nucleotide variant Pathogenic rs74315311 GRCh38 Chromosome 1, 228158615: 228158615
3 GJC2 NM_020435.3(GJC2): c.268C> T (p.Pro90Ser) single nucleotide variant Pathogenic rs74315312 GRCh37 Chromosome 1, 228345727: 228345727
4 GJC2 NM_020435.3(GJC2): c.268C> T (p.Pro90Ser) single nucleotide variant Pathogenic rs74315312 GRCh38 Chromosome 1, 228158026: 228158026
5 GJC2 NM_020435.3(GJC2): c.989delC (p.Pro330Argfs) deletion Pathogenic rs796065027 GRCh38 Chromosome 1, 228158747: 228158747
6 GJC2 NM_020435.3(GJC2): c.989delC (p.Pro330Argfs) deletion Pathogenic rs796065027 GRCh37 Chromosome 1, 228346448: 228346448
7 GJC2 NM_020435.3(GJC2): c.718C> T (p.Arg240Ter) single nucleotide variant Pathogenic rs74315313 GRCh37 Chromosome 1, 228346177: 228346177
8 GJC2 NM_020435.3(GJC2): c.718C> T (p.Arg240Ter) single nucleotide variant Pathogenic rs74315313 GRCh38 Chromosome 1, 228158476: 228158476
9 GJC2 NM_020435.3(GJC2): c.814T> G (p.Tyr272Asp) single nucleotide variant Pathogenic rs74315314 GRCh37 Chromosome 1, 228346273: 228346273
10 GJC2 NM_020435.3(GJC2): c.814T> G (p.Tyr272Asp) single nucleotide variant Pathogenic rs74315314 GRCh38 Chromosome 1, 228158572: 228158572
11 GJC2 NM_020435.3(GJC2): c.914_947del34 (p.Pro305Argfs) deletion Pathogenic rs796065028 GRCh38 Chromosome 1, 228158672: 228158705
12 GJC2 NM_020435.3(GJC2): c.914_947del34 (p.Pro305Argfs) deletion Pathogenic rs796065028 GRCh37 Chromosome 1, 228346373: 228346406
13 GJC2 NM_020435.3(GJC2): c.695_696insG (p.Tyr232Terfs) insertion Pathogenic rs796065029 GRCh38 Chromosome 1, 228158453: 228158454
14 GJC2 NM_020435.3(GJC2): c.695_696insG (p.Tyr232Terfs) insertion Pathogenic rs796065029 GRCh37 Chromosome 1, 228346154: 228346155
15 GJC2 NM_020435.3(GJC2): c.-167A> G single nucleotide variant Pathogenic rs587776888 GRCh37 Chromosome 1, 228337561: 228337561
16 GJC2 NM_020435.3(GJC2): c.-167A> G single nucleotide variant Pathogenic rs587776888 GRCh38 Chromosome 1, 228149860: 228149860
17 GJC2 NM_020435.3(GJC2): c.787G> A (p.Glu263Lys) single nucleotide variant Pathogenic rs397514734 GRCh37 Chromosome 1, 228346246: 228346246
18 GJC2 NM_020435.3(GJC2): c.787G> A (p.Glu263Lys) single nucleotide variant Pathogenic rs397514734 GRCh38 Chromosome 1, 228158545: 228158545
19 GJC2 NM_020435.3(GJC2): c.-170A> G single nucleotide variant Pathogenic rs587777496 GRCh37 Chromosome 1, 228337558: 228337558
20 GJC2 NM_020435.3(GJC2): c.-170A> G single nucleotide variant Pathogenic rs587777496 GRCh38 Chromosome 1, 228149857: 228149857
21 GJC2 NM_020435.3(GJC2): c.78delG (p.Trp27Glyfs) deletion Likely pathogenic rs886039904 GRCh37 Chromosome 1, 228345537: 228345537
22 GJC2 NM_020435.3(GJC2): c.78delG (p.Trp27Glyfs) deletion Likely pathogenic rs886039904 GRCh38 Chromosome 1, 228157836: 228157836
23 SNAP29 NM_004782.3(SNAP29): c.2T> C (p.Met1Thr) single nucleotide variant Pathogenic rs886041240 GRCh37 Chromosome 22, 21213400: 21213400
24 SNAP29 NM_004782.3(SNAP29): c.2T> C (p.Met1Thr) single nucleotide variant Pathogenic rs886041240 GRCh38 Chromosome 22, 20859112: 20859112
25 SNAP29 NM_004782.3(SNAP29): c.354dupG (p.Leu119Alafs) duplication Pathogenic rs886041263 GRCh37 Chromosome 22, 21224741: 21224741
26 SNAP29 NM_004782.3(SNAP29): c.354dupG (p.Leu119Alafs) duplication Pathogenic rs886041263 GRCh38 Chromosome 22, 20870453: 20870453
27 GJC2 NM_020435.3(GJC2): c.1175C> G (p.Ser392Cys) single nucleotide variant Likely pathogenic GRCh38 Chromosome 1, 228158933: 228158933
28 GJC2 NM_020435.3(GJC2): c.1175C> G (p.Ser392Cys) single nucleotide variant Likely pathogenic GRCh37 Chromosome 1, 228346634: 228346634

Expression for Leukodystrophy, Hypomyelinating, 2

Search GEO for disease gene expression data for Leukodystrophy, Hypomyelinating, 2.

Pathways for Leukodystrophy, Hypomyelinating, 2

Pathways related to Leukodystrophy, Hypomyelinating, 2 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.14 DLL1 GJB1 MBP
2 9.53 MBP PLP1

GO Terms for Leukodystrophy, Hypomyelinating, 2

Cellular components related to Leukodystrophy, Hypomyelinating, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 gap junction GO:0005921 9.16 GJB1 GJC2
2 myelin sheath GO:0043209 9.13 GJC2 MBP PLP1
3 connexin complex GO:0005922 8.62 GJB1 GJC2

Biological processes related to Leukodystrophy, Hypomyelinating, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 astrocyte development GO:0014002 9.16 DLL1 PLP1
2 axon ensheathment GO:0008366 8.96 MBP PLP1
3 cell communication GO:0007154 8.8 DLL1 GJB1 GJC2

Molecular functions related to Leukodystrophy, Hypomyelinating, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 gap junction channel activity GO:0005243 8.96 GJB1 GJC2
2 structural constituent of myelin sheath GO:0019911 8.62 MBP PLP1

Sources for Leukodystrophy, Hypomyelinating, 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
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32 HPO
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44 MeSH
45 MESH via Orphanet
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62 PubMed
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69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
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74 UMLS via Orphanet
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