HLD
MCID: HYP700
MIFTS: 33

Hypomyelinating Leukodystrophy (HLD)

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

Aliases & Classifications for Hypomyelinating Leukodystrophy

MalaCards integrated aliases for Hypomyelinating Leukodystrophy:

Name: Hypomyelinating Leukodystrophy 12 36 29 15
Leukodystrophy, Hypomyelinating 39
Hld 12

Classifications:



External Ids:

Disease Ontology 12 DOID:0060786
KEGG 36 H00679

Summaries for Hypomyelinating Leukodystrophy

KEGG : 36 Hypomyelinating leukodystrophies (HMLs) are disorders involving aberrant myelin formation in the central nervous system. They are clinically characterized by early onset nystagmus, impaired motor development, ataxia, choreoathetoid movements, dysarthria and progressive limb spasticity. The prototype of primary HMLs is the X-linked Pelizaeus-Merzbacher disease (PMD) caused by mutations in PLP1 encoding proteolipid protein lipophilin. Pelizaeus-Merzbacher-like disease (PMLD) is clinically similar to classical PMD but is not associated with PLP1 mutations. PMLD appears to be inherited in an autosomal recessive manner and mutations have been identified in GJC2, AIMP1, HSPD1 and so on.

MalaCards based summary : Hypomyelinating Leukodystrophy, also known as leukodystrophy, hypomyelinating, is related to spondyloepimetaphyseal dysplasia, x-linked, with hypomyelinating leukodystrophy and leukodystrophy, hypomyelinating, 3. An important gene associated with Hypomyelinating Leukodystrophy is POLR3B (RNA Polymerase III Subunit B), and among its related pathways/superpathways are ATP/ITP metabolism and Glial Cell Differentiation. Affiliated tissues include cerebellum, brain and spinal cord, and related phenotypes are behavior/neurological and mortality/aging

Disease Ontology : 12 A leukodystrophy characterized by T2 hyperintensity and T1 iso- or hyperintensity of affected white matter in the central nervous system.

Related Diseases for Hypomyelinating Leukodystrophy

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
Leukodystrophy, Hypomyelinating, 18 Leukodystrophy, Hypomyelinating, 19, Transient Infantile

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

(show top 50) (show all 98)
# Related Disease Score Top Affiliating Genes
1 spondyloepimetaphyseal dysplasia, x-linked, with hypomyelinating leukodystrophy 35.1 RAB33A AIFM1
2 leukodystrophy, hypomyelinating, 3 34.5 POLR3A AIMP1
3 leukodystrophy, hypomyelinating, 9 34.4 POLR3A GJC2 FAM126A
4 leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism 34.4 POLR3B POLR3A PLP1 GJC2
5 leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism 34.3 POLR3B POLR3A PLP1 GJC2 AIMP1
6 leukodystrophy, hypomyelinating, 10 34.2 POLR3B POLR3A
7 pelizaeus-merzbacher disease 34.1 SERPINA3 PLP1 GJC2 CNP
8 leukodystrophy, hypomyelinating, 4 34.1 POLR3A PLP1 HSPD1 GJC2 FAM126A
9 leukodystrophy, hypomyelinating, 2 34.1 PLP1 GJC2 GJB1
10 leukodystrophy, hypomyelinating, 5 34.0 PLP1 GJC2 FAM126A
11 leukodystrophy, hypomyelinating, 11 34.0 POLR3B POLR1C
12 polr3-related leukodystrophy 33.9 POLR3B POLR3A POLR1C
13 pelizaeus-merzbacher-like disease 31.3 PLP1 GJC2 GJB1 AIMP1
14 dystonia 31.1 TUBB4A PLP1 GJC2 EPRS1 DEGS1
15 leukodystrophy 30.7 TUBB4A TMEM106B SERPINA3 POLR3B POLR3A POLR1C
16 spastic paraplegia 13, autosomal dominant 30.3 HSPD1 GJC2
17 spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy 12.8
18 leukodystrophy, hypomyelinating, 6 12.4
19 leukodystrophy, hypomyelinating, 13 12.1
20 leukodystrophy, hypomyelinating, 12 12.1
21 leukodystrophy, hypomyelinating, 14 12.0
22 leukodystrophy, hypomyelinating, 16 11.9
23 leukodystrophy, hypomyelinating, 18 11.9
24 leukodystrophy, hypomyelinating, 15 11.8
25 tubb4a-related leukodystrophy 11.7
26 leukodystrophy, hypomyelinating, 17 11.3
27 leukodystrophy, hypomyelinating, 19, transient infantile 11.2
28 spastic ataxia 4 10.6 POLR3B POLR3A
29 spastic ataxia 10.6 POLR3A NKX6-2 GJC2
30 hallermann-streiff syndrome 10.6 POLR3A GJC2
31 spondyloepimetaphyseal dysplasia, x-linked 10.6 RAB33A AIFM1
32 pathologic nystagmus 10.6
33 hereditary lymphedema ic 10.6 GJC2 GJB1
34 balo concentric sclerosis 10.6 GJC2 GJB1
35 treacher collins syndrome 1 10.6 POLR3B POLR3A POLR1C
36 charcot-marie-tooth disease type x 10.6 GJC2 GJB1 AIFM1
37 megalencephalic leukoencephalopathy with subcortical cysts 2a 10.6 TUBB4A PLP1 HSPD1
38 ataxia and polyneuropathy, adult-onset 10.6
39 spastic paraplegia 75, autosomal recessive 10.5 PLP1 GJC2
40 charcot-marie-tooth disease, axonal, type 2u 10.5 GJB1 EPRS1
41 spastic paraplegia 2, x-linked 10.5 PLP1 GJC2 CNP
42 charcot-marie-tooth disease x-linked recessive 4 10.5 GJB1 AIFM1
43 spasticity 10.5
44 leukoencephalopathy with vanishing white matter 10.5 POLR3B POLR3A PLP1 GJC2
45 spastic paraplegia 44, autosomal recessive 10.5 PLP1 GJC2
46 hypomyelinating leukoencephalopathy 10.5 POLR3B POLR3A PLP1 GJC2 FAM126A
47 arteriolosclerosis 10.5 TMEM106B SERPINA3
48 wilson disease 10.5
49 hereditary neuropathies 10.5 PLP1 GJB1
50 charcot-marie-tooth disease, dominant intermediate c 10.5 GJB1 EPRS1

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



Diseases related to Hypomyelinating Leukodystrophy

Symptoms & Phenotypes for Hypomyelinating Leukodystrophy

MGI Mouse Phenotypes related to Hypomyelinating Leukodystrophy:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.97 AIFM1 AIMP1 ATRN CNP DEGS1 FAM126A
2 mortality/aging MP:0010768 9.83 AIFM1 AIMP1 ATRN CNP DEGS1 EPRS1
3 vision/eye MP:0005391 9.28 AIFM1 AIMP1 ATRN CNP GJB1 GJC2

Drugs & Therapeutics for Hypomyelinating Leukodystrophy

Search Clinical Trials , NIH Clinical Center for Hypomyelinating Leukodystrophy

Genetic Tests for Hypomyelinating Leukodystrophy

Genetic tests related to Hypomyelinating Leukodystrophy:

# Genetic test Affiliating Genes
1 Hypomyelinating Leukodystrophy 29

Anatomical Context for Hypomyelinating Leukodystrophy

MalaCards organs/tissues related to Hypomyelinating Leukodystrophy:

40
Cerebellum, Brain, Spinal Cord

Publications for Hypomyelinating Leukodystrophy

Articles related to Hypomyelinating Leukodystrophy:

(show top 50) (show all 92)
# Title Authors PMID Year
1
A recurrent de novo HSPD1 variant is associated with hypomyelinating leukodystrophy. 61
32532876 2020
2
Identification of a deep intronic POLR3A variant causing inclusion of a pseudoexon derived from an Alu element in Pol III-related leukodystrophy. 61
32483275 2020
3
A role of the frontotemporal lobar degeneration risk factor TMEM106B in myelination. 61
32572497 2020
4
CNP deficiency causes severe hypomyelinating leukodystrophy in humans. 61
32128616 2020
5
Expanding the clinical and neuroimaging features of NKX6-2-related hereditary spastic ataxia type 8. 61
32004679 2020
6
TUBB4A mutations result in both glial and neuronal degeneration in an H-ABC leukodystrophy mouse model. 61
32463361 2020
7
Rare Neurologic Disease-Associated Mutations of AIMP1 are Related with Inhibitory Neuronal Differentiation Which is Reversed by Ibuprofen. 61
32384815 2020
8
PP1C and PP2A are p70S6K Phosphatases Whose Inhibition Ameliorates HLD12-Associated Inhibition of Oligodendroglial Cell Morphological Differentiation. 61
32316234 2020
9
Recessive Ataxia Differential Diagnosis Algorithm (RADIAL) Versus Specific Niemann-Pick Type C Suspicion Indices: A Retrospective Algorithm Comparison. 61
31933160 2020
10
Genetic and phenotypic characterization of NKX6-2-related spastic ataxia and hypomyelination. 61
31509304 2020
11
Teaching NeuroImages: Hypomyelinating leukodystrophy with generalized dystonia. 61
31959690 2020
12
RARS1-related hypomyelinating leukodystrophy: Expanding the spectrum. 61
31814314 2020
13
Hypomyelinating leukodystrophy-associated mutation of RARS leads it to the lysosome, inhibiting oligodendroglial morphological differentiation. 61
31737794 2019
14
Compound heterozygous mutations in SNAP29 is associated with Pelizaeus-Merzbacher-like disorder (PMLD). 61
31748968 2019
15
Clinical spectrum of POLR3-related leukodystrophy caused by biallelic POLR1C pathogenic variants. 61
32042905 2019
16
Heterozygous Variants in the Mechanosensitive Ion Channel TMEM63A Result in Transient Hypomyelination during Infancy. 61
31587869 2019
17
Novel POLR1C mutation in RNA polymerase III-related leukodystrophy with severe myoclonus and dystonia. 61
31368241 2019
18
Late-onset phenotype associated with a homozygous GJC2 missense mutation in a Turkish family. 61
31431325 2019
19
Novel mutations in the GJC2 gene associated with Pelizaeus-Merzbacher-like disease. 61
31270756 2019
20
A hypomyelinating leukodystrophy with calcification: oculodentodigital dysplasia. 61
31240666 2019
21
The leukodystrophy mutation Polr3b R103H causes homozygote mouse embryonic lethality and impairs RNA polymerase III biogenesis. 61
31221184 2019
22
Leukodystrophy-associated POLR3A mutations down-regulate the RNA polymerase III transcript and important regulatory RNA BC200. 61
30898877 2019
23
Oculodentodigital Dysplasia: A Hypomyelinating Leukodystrophy with a Characteristic MRI Pattern of Brain Stem Involvement. 61
31048294 2019
24
Gene suppressing therapy for Pelizaeus-Merzbacher disease using artificial microRNA. 61
31092737 2019
25
Pathogenic variants in AIMP1 cause pontocerebellar hypoplasia. 61
30924036 2019
26
Hypomyelinating Leukodystrophy with Spinal Cord Involvement Caused by a Novel Variant in RARS: Report of Two Unrelated Patients. 61
30791064 2019
27
Loss of the sphingolipid desaturase DEGS1 causes hypomyelinating leukodystrophy. 61
30620337 2019
28
A study in a Polish ataxia cohort indicates genetic heterogeneity and points to MTCL1 as a novel candidate gene. 61
30548255 2019
29
Dystonia in RNA Polymerase III-Related Leukodystrophy. 61
30838315 2019
30
POLR3B-associated leukodystrophy: clinical, neuroimaging and molecular-genetic analyses in four patients: clinical heterogeneity and novel mutations in POLR3B gene. 61
31577365 2019
31
Severe TUBB4A-Related Hypomyelination With Atrophy of the Basal Ganglia and Cerebellum: Novel Neuropathological Findings. 61
30476126 2019
32
Mutation in POLR3K causes hypomyelinating leukodystrophy and abnormal ribosomal RNA regulation. 61
30584594 2018
33
Bi-allelic POLR3A Loss-of-Function Variants Cause Autosomal-Recessive Wiedemann-Rautenstrauch Syndrome. 61
30414627 2018
34
Lysosomal dysfunction in TMEM106B hypomyelinating leukodystrophy. 61
30643851 2018
35
[Hypomyelinating leukodystrophy type 6. Clinical and neuroimaging key features in the detection of a new case]. 61
30350845 2018
36
[The importance of semiology and biochemistry in the diagnostic management of a peroxisomal biogenesis disorder]. 61
30289153 2018
37
Leukodystrophy with disorders of sex development due to WT1 mutations. 61
29801916 2018
38
The recurrent mutation in TMEM106B also causes hypomyelinating leukodystrophy in China and is a CpG hotspot. 61
29444210 2018
39
Reply: The recurrent mutation in TMEM106B also causes hypomyelinating leukodystrophy in China and is a CpG hotspot. 61
29444246 2018
40
Bi-allelic Mutations in EPRS, Encoding the Glutamyl-Prolyl-Aminoacyl-tRNA Synthetase, Cause a Hypomyelinating Leukodystrophy. 61
29576217 2018
41
A novel homozygous mutation in POLR3A gene causing 4H syndrome: a case report. 61
29618326 2018
42
Homozygosity for a nonsense variant in AIMP2 is associated with a progressive neurodevelopmental disorder with microcephaly, seizures, and spastic quadriparesis. 61
29215095 2018
43
Independent occurrence of de novo HSPD1 and HIP1 variants in brothers with different neurological disorders - leukodystrophy and autism. 61
30083362 2018
44
Hypomyelinating disorders in China: The clinical and genetic heterogeneity in 119 patients. 61
29451896 2018
45
A recurrent de novo mutation in TMEM106B causes hypomyelinating leukodystrophy. 61
29186371 2017
46
X-linked hypomyelination with spondylometaphyseal dysplasia (H-SMD) associated with mutations in AIFM1. 61
28842795 2017
47
[Clinical manifestation and gene analyses of 15 patients with intellectual disability or developmental delay complicated with congenital nystagmus]. 61
29141312 2017
48
Biallelic mutations in the homeodomain of NKX6-2 underlie a severe hypomyelinating leukodystrophy. 61
28969374 2017
49
Hypomyelinating leukodystrophy associated with a deleterious mutation in the ATRN gene. 61
28493104 2017
50
Hypomorphic mutations in POLR3A are a frequent cause of sporadic and recessive spastic ataxia. 61
28459997 2017

Variations for Hypomyelinating Leukodystrophy

Expression for Hypomyelinating Leukodystrophy

Search GEO for disease gene expression data for Hypomyelinating Leukodystrophy.

Pathways for Hypomyelinating Leukodystrophy

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

# Super pathways Score Top Affiliating Genes
1 11.06 POLR3B POLR3A POLR1C
2 9.53 PLP1 CNP

GO Terms for Hypomyelinating Leukodystrophy

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

# Name GO ID Score Top Affiliating Genes
1 connexin complex GO:0005922 9.26 GJC2 GJB1
2 aminoacyl-tRNA synthetase multienzyme complex GO:0017101 9.16 EPRS1 AIMP1
3 RNA polymerase III complex GO:0005666 9.13 POLR3B POLR3A POLR1C
4 myelin sheath GO:0043209 8.92 TUBB4A PLP1 GJC2 CNP

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

# Name GO ID Score Top Affiliating Genes
1 transcription, DNA-templated GO:0006351 9.54 POLR3B POLR3A POLR1C
2 response to toxic substance GO:0009636 9.5 GJC2 CNP AIFM1
3 myelination GO:0042552 9.33 PLP1 FAM126A ATRN
4 central nervous system myelination GO:0022010 9.26 PLP1 NKX6-2
5 positive regulation of type I interferon production GO:0032481 9.13 POLR3B POLR3A POLR1C
6 protein import into mitochondrial intermembrane space GO:0045041 8.62 HSPD1 AIFM1

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

# Name GO ID Score Top Affiliating Genes
1 gap junction channel activity GO:0005243 8.96 GJC2 GJB1
2 DNA-directed 5'-3' RNA polymerase activity GO:0003899 8.8 POLR3B POLR3A POLR1C

Sources for Hypomyelinating Leukodystrophy

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11 DGIdb
17 EFO
18 ExPASy
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31 HPO
32 ICD10
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61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
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70 Tocris
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72 UMLS via Orphanet
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