HLD12
MCID: LKD023
MIFTS: 37

Leukodystrophy, Hypomyelinating, 12 (HLD12)

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

Aliases & Classifications for Leukodystrophy, Hypomyelinating, 12

MalaCards integrated aliases for Leukodystrophy, Hypomyelinating, 12:

Name: Leukodystrophy, Hypomyelinating, 12 56 73 29 6
Hld12 56 12 73
Hypomyelinating Leukodystrophy 12 12 15
Vps11-Related Autosomal Recessive Hypomyelinating Leukoencephalopathy 58
Vps11-Related Autosomal Recessive Hypomyelinating Leukodystrophy 58

Characteristics:

OMIM:

56
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 : 56 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)

MalaCards based summary : Leukodystrophy, Hypomyelinating, 12, also known as hld12, is related to neuropathy, hereditary sensory and autonomic, type i, with cough and gastroesophageal reflux and charcot-marie-tooth disease, axonal, type 2l. 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 Phagosome. Affiliated tissues include brain, and 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

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

(show all 15)
# Related Disease Score Top Affiliating Genes
1 neuropathy, hereditary sensory and autonomic, type i, with cough and gastroesophageal reflux 10.1 RAB7B RAB7A
2 charcot-marie-tooth disease, axonal, type 2l 10.1 RAB7B RAB7A
3 charcot-marie-tooth disease, dominant intermediate b 10.1 RAB7B RAB7A
4 hereditary motor and sensory neuropathy, type iic 10.1 RAB7B RAB7A
5 charcot-marie-tooth disease, axonal, type 2b 10.1 RAB7B RAB7A
6 charcot-marie-tooth disease, type 4j 10.1 RAB7B RAB7A
7 vici syndrome 10.0 RAB7B RAB7A
8 charcot-marie-tooth disease, demyelinating, type 1c 10.0 RAB7B RAB7A
9 legionnaire disease 10.0 RAB7B RAB7A
10 warburg micro syndrome 10.0 RAB7B RAB7A
11 c syndrome 9.9 RAB7B RAB7A
12 carpenter syndrome 1 9.9 RAB7B RAB7A
13 cataract 8, multiple types 9.9 RAB7B RAB7A EEA1
14 niemann-pick disease, type c1 9.8 RAB7B RAB7A
15 charcot-marie-tooth disease, axonal, type 2e 9.4 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 39)
# 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 central hypotonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0011398
5 cerebral visual impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0100704
6 sensorineural hearing impairment 58 31 frequent (33%) Frequent (79-30%) HP:0000407
7 optic atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0000648
8 spasticity 58 31 frequent (33%) Frequent (79-30%) HP:0001257
9 absent speech 58 31 frequent (33%) Frequent (79-30%) HP:0001344
10 growth delay 58 31 frequent (33%) Frequent (79-30%) HP:0001510
11 multiple joint contractures 58 31 frequent (33%) Frequent (79-30%) HP:0002828
12 constipation 58 31 frequent (33%) Frequent (79-30%) HP:0002019
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 coarse facial features 58 Excluded (0%)
25 hearing impairment 31 HP:0000365
26 seizures 58 Very frequent (99-80%)
27 flexion contracture 31 HP:0001371
28 developmental stagnation 31 HP:0007281
29 reduced visual acuity 31 HP:0007663
30 severe global developmental delay 31 HP:0011344
31 focal impaired awareness seizure 31 HP:0002384
32 postnatal microcephaly 31 HP:0005484
33 hepatosplenomegaly 58 Excluded (0%)
34 dysautonomia 58 Frequent (79-30%)
35 muscular hypotonia of the trunk 31 HP:0008936
36 cerebral hypomyelination 31 HP:0006808
37 temperature instability 31 HP:0005968
38 febrile seizures 58 Frequent (79-30%)
39 delayed myelination 31 HP:0012448

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
intellectual disability
spasticity
delayed myelination
autonomic dysfunction
delayed psychomotor development
more
Abdomen Gastrointestinal:
constipation
oromotor dysfunction

Growth Other:
poor overall growth

Head And Neck Mouth:
oromotor dysfunction

Head And Neck Eyes:
optic atrophy
cortical visual impairment

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

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

26 (show all 13)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-137 9.44 RAB7A
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-147 9.44 PPT2
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-148 9.44 VPS11
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-157 9.44 VPS11
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-161 9.44 VPS11
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-173 9.44 VPS11
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-194 9.44 PPT2
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-213 9.44 PPT2
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-34 9.44 VPS11
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-63 9.44 VPS11
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-73 9.44 PPT2
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-82 9.44 VPS11
13 Decreased shRNA abundance (Z-score < -2) GR00366-A-85 9.44 PPT2

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

MalaCards organs/tissues related to Leukodystrophy, Hypomyelinating, 12:

40
Brain

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. 56 6
27120463 2016
2
Hypomyelination and developmental delay associated with VPS11 mutation in Ashkenazi-Jewish patients. 56 6
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 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

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:

# Super pathways Score Top Affiliating Genes
1 11.75 VPS11 RAB7B RAB7A
2 11.51 RAB7B RAB7A EEA1
3 11.27 RPS6KB1 RAB7B RAB7A
4 11.08 RAB7B RAB7A
5 11.01 RPS6KB1 PTPA
6
Show member pathways
10.91 RAB7A EEA1
7
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 cytoplasmic vesicle GO:0031410 9.62 VPS11 RAB7B RAB7A EEA1
2 endosome GO:0005768 9.56 VPS11 RAB7B RAB7A EEA1
3 late endosome GO:0005770 9.33 VPS11 RAB7B RAB7A
4 lysosome GO:0005764 9.26 VPS11 RAB7B RAB7A PPT2
5 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 early endosome to late endosome transport GO:0045022 9.26 RAB7A EEA1
2 phagosome-lysosome fusion GO:0090385 9.16 RAB7B RAB7A
3 vacuole organization GO:0007033 8.96 VPS11 NDP
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 protein phosphatase 1 binding GO:0008157 8.62 STAU1 PPP1CC

Sources for Leukodystrophy, Hypomyelinating, 12

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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