HLD
MCID: HYP700
MIFTS: 35

Hypomyelinating Leukodystrophy (HLD)

Categories: Ear diseases, Eye diseases, Fetal diseases, Genetic diseases, Muscle 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 leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism 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 eye, spinal cord and cerebellum, and related phenotypes are Decreased viability and Decreased viability

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
Leukodystrophy, Hypomyelinating, 20 Leukodystrophy, Hypomyelinating, 21

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

(show top 50) (show all 109)
# Related Disease Score Top Affiliating Genes
1 leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism 33.2 POLR3B POLR3A GJC2
2 leukodystrophy, hypomyelinating, 3 33.2 POLR3A AIMP1
3 leukodystrophy, hypomyelinating, 9 33.0 RARS1 POLR3A GJC2 FAM126A
4 leukodystrophy, hypomyelinating, 10 33.0 PYCR2 POLR3B POLR3A
5 leukodystrophy, hypomyelinating, 2 33.0 PLP1 GJC2 GJB1
6 leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism 33.0 POLR3B POLR3A PLP1 GJC2 AIMP1
7 leukodystrophy, hypomyelinating, 5 32.9 PLP1 GJC2 FAM126A
8 leukodystrophy, hypomyelinating, 4 32.8 POLR3A PLP1 HSPD1 GJC2 FAM126A
9 pelizaeus-merzbacher disease 32.6 SERPINA3 RARS1 PLP1 GJC2 CNP
10 polr3-related leukodystrophy 32.4 POLR3B POLR3A POLR1C
11 pelizaeus-merzbacher-like disease 30.7 POLR3A PLP1 HSPD1 GJC2 GJB1 AIMP1
12 leukodystrophy 30.6 TUBB4A TMEM106B RARS1 PYCR2 POLR3B POLR3A
13 x-linked recessive disease 30.4 SERPINA3 PLP1 EPRS1
14 spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy 11.8
15 spondyloepimetaphyseal dysplasia, x-linked, with hypomyelinating leukodystrophy 11.8
16 leukodystrophy, hypomyelinating, 6 11.7
17 leukodystrophy, hypomyelinating, 13 11.6
18 leukodystrophy, hypomyelinating, 12 11.6
19 leukodystrophy, hypomyelinating, 11 11.6
20 leukodystrophy, hypomyelinating, 14 11.5
21 leukodystrophy, hypomyelinating, 20 11.5
22 leukodystrophy, hypomyelinating, 18 11.4
23 leukodystrophy, hypomyelinating, 15 11.3
24 leukodystrophy, hypomyelinating, 16 11.3
25 leukodystrophy, hypomyelinating, 17 11.2
26 tubb4a-related leukodystrophy 11.2
27 leukodystrophy, hypomyelinating, 21 11.1
28 leukodystrophy, hypomyelinating, 19, transient infantile 11.1
29 pathologic nystagmus 10.5
30 ataxia and polyneuropathy, adult-onset 10.5
31 spastic ataxia 10.5 POLR3A NKX6-2 GJC2
32 spastic ataxia 4 10.4 POLR3B POLR3A
33 dystonia 10.4
34 spasticity 10.4
35 treacher collins syndrome 1 10.4 POLR3B POLR3A POLR1C
36 hereditary lymphedema ic 10.4 GJC2 GJB1
37 charcot-marie-tooth disease type x 10.4 GJC2 GJB1 AIFM1
38 boucher-neuhauser syndrome 10.4 POLR3B POLR3A
39 hallermann-streiff syndrome 10.4 GJC2 GJB1
40 torsion dystonia 4 10.4 TUBB4A PLP1 HSPD1
41 megalencephalic leukoencephalopathy with subcortical cysts 2a 10.4 TUBB4A PLP1 HSPD1
42 robinow syndrome, autosomal recessive 1 10.4 RARS1 EPRS1 AIMP1
43 robinow syndrome 10.4 RARS1 EPRS1 AIMP1
44 spastic paraplegia 44, autosomal recessive 10.4 PLP1 GJC2 GJB1
45 spastic paraplegia 75, autosomal recessive 10.3 PLP1 GJC2
46 spastic paraplegia 2, x-linked 10.3 PLP1 GJC2 CNP
47 charcot-marie-tooth disease, axonal, type 2u 10.3 GJB1 EPRS1
48 cardiomyopathy, familial hypertrophic, 3 10.3 SERPINA3 ATRN
49 hypomyelinating leukoencephalopathy 10.3 POLR3B POLR3A PLP1 GJC2 FAM126A
50 leukoencephalopathy with vanishing white matter 10.3 POLR3B POLR3A POLR1C PLP1 GJC2

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



Diseases related to Hypomyelinating Leukodystrophy

Symptoms & Phenotypes for Hypomyelinating Leukodystrophy

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

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00055-A-1 9.68 GJB1
2 Decreased viability GR00055-A-2 9.68 GJB1
3 Decreased viability GR00240-S-1 9.68 EPRS1 POLR3B
4 Decreased viability GR00249-S 9.68 CNP GJB1 POLR1C PYCR2 SERPINA3
5 Decreased viability GR00301-A 9.68 CNP
6 Decreased viability GR00381-A-1 9.68 AIFM1 PYCR2
7 Decreased viability GR00386-A-1 9.68 CNP POLR3B
8 Decreased viability GR00402-S-2 9.68 AIMP1 DEGS1 EPRS1 GJB1 POLR1C POLR3A

MGI Mouse Phenotypes related to Hypomyelinating Leukodystrophy:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.39 AIFM1 AIMP1 ATRN CNP DEGS1 FAM126A
2 mortality/aging MP:0010768 10.22 AIFM1 AIMP1 ATRN CNP DEGS1 EPRS1
3 growth/size/body region MP:0005378 10.21 AIFM1 AIMP1 ATRN CNP DEGS1 EPRS1
4 cellular MP:0005384 10.14 AIFM1 CNP DEGS1 EPRS1 GJB1 GJC2
5 nervous system MP:0003631 9.93 AIFM1 ATRN CNP GJB1 GJC2 HSPD1
6 muscle MP:0005369 9.86 AIFM1 ATRN CNP DEGS1 HSPD1 PLP1
7 skeleton MP:0005390 9.61 ATRN CNP DEGS1 EPRS1 PLP1 POLR3A
8 vision/eye MP:0005391 9.28 AIFM1 ATRN CNP GJB1 GJC2 NKX6-2

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
Eye, Spinal Cord, Cerebellum, Brain

Publications for Hypomyelinating Leukodystrophy

Articles related to Hypomyelinating Leukodystrophy:

(show top 50) (show all 112)
# Title Authors PMID Year
1
AIFM1-associated X-linked spondylometaphyseal dysplasia with cerebral hypomyelination. 61
33439541 2021
2
Peripheral nerves are involved in hypomyelinating leukodystrophy-3 caused by a homozygous AIMP1 variant. 61
33402283 2021
3
Combined Genome, Transcriptome and Metabolome Analysis in the Diagnosis of Childhood Cerebellar Ataxia. 61
33804237 2021
4
Hypomyelinating Leukodystrophy 15 (HLD15)-Associated Mutation of EPRS1 Leads to Its Polymeric Aggregation in Rab7-Positive Vesicle Structures, Inhibiting Oligodendroglial Cell Morphological Differentiation. 61
33805425 2021
5
A hypomyelinating leukodystrophy in German Shepherd dogs. 61
33734486 2021
6
Physiological and pathological functions of TMEM106B: a gene associated with brain aging and multiple brain disorders. 61
33386471 2021
7
Genetic analysis of Pycr1 and Pycr2 in mice. 61
33734376 2021
8
De novo stop-loss variants in CLDN11 cause hypomyelinating leukodystrophy. 61
33313762 2021
9
Disease variants of human Δ1-pyrroline-5-carboxylate reductase 2 (PYCR2). 61
33771508 2021
10
Genetic analysis of 20 patients with hypomyelinating leukodystrophy by trio-based whole-exome sequencing. 61
33597727 2021
11
Functional characterization of Polr3a hypomyelinating leukodystrophy mutations in the S. cerevisiae homolog, RPC160. 61
33148458 2021
12
Expanding the Clinical and Mutational Spectrum of the PLP1-Related Hypomyelination of Early Myelinated Structures (HEMS). 61
33450882 2021
13
De novo variants in POLR3B cause ataxia, spasticity, and demyelinating neuropathy. 61
33417887 2021
14
Novel Mutations in NPC1 are Associated with Pelizaeus-Merzbacher-Like Disease: A Case Report. 61
33727856 2021
15
Neurodevelopmental regression, severe generalized dystonia, and metabolic acidosis caused by POLR3A mutations. 61
33134517 2020
16
POLR1C variants dysregulate splicing and cause hypomyelinating leukodystrophy. 61
33134519 2020
17
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
18
A Novel CCT5 Missense Variant Associated with Early Onset Motor Neuropathy. 61
33076433 2020
19
A hypomyelinating leukodystrophy with calcification: oculodentodigital dysplasia. 61
31240666 2020
20
A recurrent TMEM106B mutation in hypomyelinating leukodystrophy: A rapid diagnostic assay. 61
32595021 2020
21
PYRC2-Related Hypomyelinating Leukodystrophy: More to This Than Meets the Eye. 61
32645307 2020
22
A role of the frontotemporal lobar degeneration risk factor TMEM106B in myelination. 61
32572497 2020
23
A recurrent de novo HSPD1 variant is associated with hypomyelinating leukodystrophy. 61
32532876 2020
24
Expanding the clinical and neuroimaging features of NKX6-2-related hereditary spastic ataxia type 8. 61
32004679 2020
25
TUBB4A mutations result in both glial and neuronal degeneration in an H-ABC leukodystrophy mouse model. 61
32463361 2020
26
Rare Neurologic Disease-Associated Mutations of AIMP1 are Related with Inhibitory Neuronal Differentiation Which is Reversed by Ibuprofen. 61
32384815 2020
27
CNP deficiency causes severe hypomyelinating leukodystrophy in humans. 61
32128616 2020
28
PP1C and PP2A are p70S6K Phosphatases Whose Inhibition Ameliorates HLD12-Associated Inhibition of Oligodendroglial Cell Morphological Differentiation. 61
32316234 2020
29
Recessive Ataxia Differential Diagnosis Algorithm (RADIAL) Versus Specific Niemann-Pick Type C Suspicion Indices: A Retrospective Algorithm Comparison. 61
31933160 2020
30
Genetic and phenotypic characterization of NKX6-2-related spastic ataxia and hypomyelination. 61
31509304 2020
31
POLR3-Related Leukodystrophy: Exploring Potential Therapeutic Approaches. 61
33633543 2020
32
Teaching NeuroImages: Hypomyelinating leukodystrophy with generalized dystonia. 61
31959690 2020
33
RARS1-related hypomyelinating leukodystrophy: Expanding the spectrum. 61
31814314 2020
34
Clinical spectrum of POLR3-related leukodystrophy caused by biallelic POLR1C pathogenic variants. 61
32042905 2019
35
Compound heterozygous mutations in SNAP29 is associated with Pelizaeus-Merzbacher-like disorder (PMLD). 61
31748968 2019
36
Hypomyelinating leukodystrophy-associated mutation of RARS leads it to the lysosome, inhibiting oligodendroglial morphological differentiation. 61
31737794 2019
37
Heterozygous Variants in the Mechanosensitive Ion Channel TMEM63A Result in Transient Hypomyelination during Infancy. 61
31587869 2019
38
Novel POLR1C mutation in RNA polymerase III-related leukodystrophy with severe myoclonus and dystonia. 61
31368241 2019
39
Late-onset phenotype associated with a homozygous GJC2 missense mutation in a Turkish family. 61
31431325 2019
40
Novel mutations in the GJC2 gene associated with Pelizaeus-Merzbacher-like disease. 61
31270756 2019
41
The leukodystrophy mutation Polr3b R103H causes homozygote mouse embryonic lethality and impairs RNA polymerase III biogenesis. 61
31221184 2019
42
Leukodystrophy-associated POLR3A mutations down-regulate the RNA polymerase III transcript and important regulatory RNA BC200. 61
30898877 2019
43
Pathogenic variants in AIMP1 cause pontocerebellar hypoplasia. 61
30924036 2019
44
Gene suppressing therapy for Pelizaeus-Merzbacher disease using artificial microRNA. 61
31092737 2019
45
Oculodentodigital Dysplasia: A Hypomyelinating Leukodystrophy with a Characteristic MRI Pattern of Brain Stem Involvement. 61
31048294 2019
46
Hypomyelinating Leukodystrophy with Spinal Cord Involvement Caused by a Novel Variant in RARS: Report of Two Unrelated Patients. 61
30791064 2019
47
A study in a Polish ataxia cohort indicates genetic heterogeneity and points to MTCL1 as a novel candidate gene. 61
30548255 2019
48
Loss of the sphingolipid desaturase DEGS1 causes hypomyelinating leukodystrophy. 61
30620337 2019
49
Dystonia in RNA Polymerase III-Related Leukodystrophy. 61
30838315 2019
50
Severe TUBB4A-Related Hypomyelination With Atrophy of the Basal Ganglia and Cerebellum: Novel Neuropathological Findings. 61
30476126 2019

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 RNA polymerase III complex GO:0005666 9.33 POLR3B POLR3A POLR1C
2 connexin complex GO:0005922 9.26 GJC2 GJB1
3 aminoacyl-tRNA synthetase multienzyme complex GO:0017101 9.13 RARS1 EPRS1 AIMP1
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 9.61 POLR3B POLR3A POLR1C
2 response to toxic substance GO:0009636 9.54 GJC2 CNP AIFM1
3 positive regulation of type I interferon production GO:0032481 9.5 POLR3B POLR3A POLR1C
4 myelination GO:0042552 9.43 PLP1 FAM126A ATRN
5 central nervous system myelination GO:0022010 9.4 PLP1 NKX6-2
6 tRNA aminoacylation for protein translation GO:0006418 9.33 RARS1 EPRS1 AIMP1
7 protein import into mitochondrial intermembrane space GO:0045041 8.96 HSPD1 AIFM1
8 positive regulation of calcium ion transmembrane transport GO:1904427 8.62 PLP1 GJC2

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

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
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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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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