HLD12
MCID: LKD023
MIFTS: 38

Leukodystrophy, Hypomyelinating, 12 (HLD12)

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

Aliases & Classifications for Leukodystrophy, Hypomyelinating, 12

MalaCards integrated aliases for Leukodystrophy, Hypomyelinating, 12:

Name: Leukodystrophy, Hypomyelinating, 12 57 73 29 6
Hld12 57 12 73
Hypomyelinating Leukodystrophy 12 12 15
Vps11-Related Autosomal Recessive Hypomyelinating Leukoencephalopathy 58
Vps11-Related Autosomal Recessive Hypomyelinating Leukodystrophy 58

Characteristics:

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal recessive

Miscellaneous:
onset between 3 and 8 months of age
increased frequency in ashkenazi jewish population


HPO:

31
leukodystrophy, hypomyelinating, 12:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases


Summaries for Leukodystrophy, Hypomyelinating, 12

OMIM® : 57 Hypomyelinating leukodystrophy-12 is an autosomal recessive neurologic disorder characterized by severely delayed or even lack of psychomotor development that becomes apparent in the first months of life. Patients are markedly disabled, with acquired microcephaly, lack of speech, and often lack of spontaneous movement due to hypotonia and spasticity. Brain imaging shows delayed myelination (summary by Edvardson et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of HLD, see 312080. (616683) (Updated 05-Mar-2021)

MalaCards based summary : Leukodystrophy, Hypomyelinating, 12, also known as hld12, is related to pelizaeus-merzbacher disease and autosomal recessive disease. An important gene associated with Leukodystrophy, Hypomyelinating, 12 is VPS11 (VPS11 Core Subunit Of CORVET And HOPS Complexes), and among its related pathways/superpathways are Salmonella infection (KEGG) and Amoebiasis. Related phenotypes are intellectual disability and global developmental delay

Disease Ontology : 12 A hypomyelinating leukodystrophy characterized by autosomal recessive inheritance of severely delayed or even lack of psychomotor development that becomes apparent in the first months of life, acquired microcephaly and delayed myelination that has material basis in homozygous mutation in the VPS11 gene on chromosome 11q23.

UniProtKB/Swiss-Prot : 73 Leukodystrophy, hypomyelinating, 12: An autosomal recessive neurologic disorder characterized by developmental delay, spasticity, truncal hypotonia, acquired microcephaly, intellectual disability with variable seizure disorder, accompanied by thin corpus callosum, paucity of white matter and delayed myelination.

Related Diseases for Leukodystrophy, Hypomyelinating, 12

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

Diseases related to Leukodystrophy, Hypomyelinating, 12 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 23)
# Related Disease Score Top Affiliating Genes
1 pelizaeus-merzbacher disease 9.9
2 autosomal recessive disease 9.9
3 hypomyelinating leukodystrophy 9.9
4 leukodystrophy 9.9
5 neuropathy, hereditary sensory and autonomic, type i, with cough and gastroesophageal reflux 9.9 RAB7B RAB7A
6 neuropathy, hereditary sensory, type id 9.9 RAB7B RAB7A
7 charcot-marie-tooth disease, axonal, type 2l 9.9 RAB7B RAB7A
8 charcot-marie-tooth disease, dominant intermediate b 9.9 RAB7B RAB7A
9 hereditary motor and sensory neuropathy, type iic 9.9 RAB7B RAB7A
10 charcot-marie-tooth disease, axonal, type 2b 9.9 RAB7B RAB7A
11 charcot-marie-tooth disease, type 4j 9.9 RAB7B RAB7A
12 vici syndrome 9.9 RAB7B RAB7A
13 legionnaire disease 9.8 RAB7B RAB7A
14 charcot-marie-tooth disease, type 4b2 9.8 RAB7B RAB7A
15 warburg micro syndrome 9.8 RAB7B RAB7A
16 c syndrome 9.8 RAB7B RAB7A
17 niemann-pick disease, type c1 9.7 RAB7B RAB7A
18 cataract 8, multiple types 9.7 RAB7B RAB7A EEA1
19 charcot-marie-tooth disease, demyelinating, type 1c 9.7 RAB7B RAB7A EEA1
20 hermansky-pudlak syndrome 9.6 RAB7B RAB7A EEA1
21 griscelli syndrome 9.6 RAB7B RAB7A
22 charcot-marie-tooth disease, axonal, type 2e 9.5 RAB7B RAB7A EEA1
23 amyotrophic lateral sclerosis 1 9.3 VPS11 RAB7B RAB7A EEA1

Graphical network of the top 20 diseases related to Leukodystrophy, Hypomyelinating, 12:



Diseases related to Leukodystrophy, Hypomyelinating, 12

Symptoms & Phenotypes for Leukodystrophy, Hypomyelinating, 12

Human phenotypes related to Leukodystrophy, Hypomyelinating, 12:

58 31 (show all 40)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001249
2 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001263
3 microcephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0000252
4 cerebral visual impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0100704
5 hypotonia 31 hallmark (90%) HP:0001252
6 spasticity 58 31 frequent (33%) Frequent (79-30%) HP:0001257
7 constipation 58 31 frequent (33%) Frequent (79-30%) HP:0002019
8 sensorineural hearing impairment 58 31 frequent (33%) Frequent (79-30%) HP:0000407
9 optic atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0000648
10 absent speech 58 31 frequent (33%) Frequent (79-30%) HP:0001344
11 growth delay 58 31 frequent (33%) Frequent (79-30%) HP:0001510
12 multiple joint contractures 58 31 frequent (33%) Frequent (79-30%) HP:0002828
13 ventriculomegaly 58 31 frequent (33%) Frequent (79-30%) HP:0002119
14 hypoplasia of the corpus callosum 58 31 frequent (33%) Frequent (79-30%) HP:0002079
15 abnormality of the periventricular white matter 58 31 frequent (33%) Frequent (79-30%) HP:0002518
16 poor speech 58 31 frequent (33%) Frequent (79-30%) HP:0002465
17 neurogenic bladder 58 31 frequent (33%) Frequent (79-30%) HP:0000011
18 diffuse white matter abnormalities 58 31 frequent (33%) Frequent (79-30%) HP:0007204
19 delayed cns myelination 58 31 frequent (33%) Frequent (79-30%) HP:0002188
20 oromotor apraxia 58 31 frequent (33%) Frequent (79-30%) HP:0007301
21 abnormal autonomic nervous system physiology 31 frequent (33%) HP:0012332
22 febrile seizure (within the age range of 3 months to 6 years) 31 frequent (33%) HP:0002373
23 cerebellar atrophy 58 31 very rare (1%) Very rare (<4-1%) HP:0001272
24 seizures 58 Very frequent (99-80%)
25 dysautonomia 58 Frequent (79-30%)
26 coarse facial features 58 Excluded (0%)
27 hearing impairment 31 HP:0000365
28 flexion contracture 31 HP:0001371
29 developmental stagnation 31 HP:0007281
30 reduced visual acuity 31 HP:0007663
31 severe global developmental delay 31 HP:0011344
32 focal impaired awareness seizure 31 HP:0002384
33 postnatal microcephaly 31 HP:0005484
34 hepatosplenomegaly 58 Excluded (0%)
35 central hypotonia 58 Very frequent (99-80%)
36 muscular hypotonia of the trunk 31 HP:0008936
37 cerebral hypomyelination 31 HP:0006808
38 temperature instability 31 HP:0005968
39 febrile seizures 58 Frequent (79-30%)
40 delayed myelination 31 HP:0012448

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Neurologic Central Nervous System:
intellectual disability
spasticity
delayed myelination
autonomic dysfunction
delayed psychomotor development
more
Head And Neck Eyes:
optic atrophy
cortical visual impairment

Growth Other:
poor overall growth

Head And Neck Mouth:
oromotor dysfunction

Abdomen Gastrointestinal:
constipation
oromotor dysfunction

Head And Neck Ears:
hearing loss

Muscle Soft Tissue:
truncal hypotonia

Head And Neck Head:
microcephaly, acquired (up to -3 sd)

Clinical features from OMIM®:

616683 (Updated 05-Mar-2021)

Drugs & Therapeutics for Leukodystrophy, Hypomyelinating, 12

Search Clinical Trials , NIH Clinical Center for Leukodystrophy, Hypomyelinating, 12

Genetic Tests for Leukodystrophy, Hypomyelinating, 12

Genetic tests related to Leukodystrophy, Hypomyelinating, 12:

# Genetic test Affiliating Genes
1 Leukodystrophy, Hypomyelinating, 12 29 VPS11

Anatomical Context for Leukodystrophy, Hypomyelinating, 12

Publications for Leukodystrophy, Hypomyelinating, 12

Articles related to Leukodystrophy, Hypomyelinating, 12:

# Title Authors PMID Year
1
A Founder Mutation in VPS11 Causes an Autosomal Recessive Leukoencephalopathy Linked to Autophagic Defects. 6 57
27120463 2016
2
Hypomyelination and developmental delay associated with VPS11 mutation in Ashkenazi-Jewish patients. 6 57
26307567 2015
3
PP1C and PP2A are p70S6K Phosphatases Whose Inhibition Ameliorates HLD12-Associated Inhibition of Oligodendroglial Cell Morphological Differentiation. 61
32316234 2020

Variations for Leukodystrophy, Hypomyelinating, 12

ClinVar genetic disease variations for Leukodystrophy, Hypomyelinating, 12:

6
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 VPS11 NM_021729.5(VPS11):c.2536T>G (p.Cys846Gly) SNV Likely pathogenic 218366 rs34757931 11:118951899-118951899 11:119081189-119081189
2 VPS11 NM_021729.5(VPS11):c.2557A>G (p.Ser853Gly) SNV Uncertain significance 635068 rs1565746289 11:118951920-118951920 11:119081210-119081210
3 VPS11 NM_021729.6(VPS11):c.2615_2620del (p.Arg872_Ala873del) Deletion Uncertain significance 976215 11:118951976-118951981 11:119081266-119081271

UniProtKB/Swiss-Prot genetic disease variations for Leukodystrophy, Hypomyelinating, 12:

73
# Symbol AA change Variation ID SNP ID
1 VPS11 p.Cys846Gly VAR_076393

Expression for Leukodystrophy, Hypomyelinating, 12

Search GEO for disease gene expression data for Leukodystrophy, Hypomyelinating, 12.

Pathways for Leukodystrophy, Hypomyelinating, 12

Pathways related to Leukodystrophy, Hypomyelinating, 12 according to GeneCards Suite gene sharing:

(show all 12)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.28 VPS11 RAB7B RAB7A
2 11.52 RAB7B RAB7A
3 11.51 RAB7B RAB7A EEA1
4
Show member pathways
11.45 PTPA PPP1CC
5 11.43 RAB7B RAB7A
6 11.27 RAB7B RAB7A
7 11.27 RPS6KB1 RAB7B RAB7A
8 11.22 RAB7B RAB7A
9 11.04 RAB7B RAB7A
10 10.97 RPS6KB1 PTPA
11
Show member pathways
10.85 RAB7A EEA1
12
Show member pathways
10.84 RPS6KB1 PTPA PPP1CC

GO Terms for Leukodystrophy, Hypomyelinating, 12

Cellular components related to Leukodystrophy, Hypomyelinating, 12 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lysosome GO:0005764 9.58 VPS11 RAB7B RAB7A
2 cytoplasmic vesicle GO:0031410 9.56 VPS11 RAB7B RAB7A EEA1
3 endosome GO:0005768 9.46 VPS11 RAB7B RAB7A EEA1
4 phagocytic vesicle GO:0045335 9.37 RAB7B RAB7A
5 phagocytic vesicle membrane GO:0030670 9.32 RAB7B RAB7A
6 late endosome GO:0005770 9.13 VPS11 RAB7B RAB7A
7 late endosome membrane GO:0031902 8.8 VPS11 RAB7B RAB7A

Biological processes related to Leukodystrophy, Hypomyelinating, 12 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cellular response to interferon-gamma GO:0071346 9.26 RPS6KB1 RAB7B
2 early endosome to late endosome transport GO:0045022 9.16 RAB7A EEA1
3 phagosome-lysosome fusion GO:0090385 8.96 RAB7B RAB7A
4 endosome to lysosome transport GO:0008333 8.8 VPS11 RAB7B RAB7A

Molecular functions related to Leukodystrophy, Hypomyelinating, 12 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleotide binding GO:0000166 9.35 VPS11 RPS6KB1 RAB7B RAB7A PTPA
2 protein phosphatase 2A binding GO:0051721 8.62 RPS6KB1 PTPA

Sources for Leukodystrophy, Hypomyelinating, 12

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
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