MCID: CHR544
MIFTS: 28

Charcot-Marie-Tooth Disease, Axonal, Type 2w

Categories: Genetic diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Charcot-Marie-Tooth Disease, Axonal, Type 2w

MalaCards integrated aliases for Charcot-Marie-Tooth Disease, Axonal, Type 2w:

Name: Charcot-Marie-Tooth Disease, Axonal, Type 2w 57 75 29 6
Cmt2w 57 12 59 75
Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type 2w 57 75
Charcot-Marie-Tooth Disease, Axonal Type 2w 12 15
Charcot-Marie-Tooth Neuropathy, Type 2w 57 75
Autosomal Dominant Charcot-Marie-Tooth Disease Type 2 Due to Hars Mutation 59
Autosomal Dominant Axonal Charcot-Marie-Tooth Disease Type 2w 12
Autosomal Dominant Charcot-Marie-Tooth Disease Type 2w 59
Charcot-Marie-Tooth Neuropathy Type 2w 12
Charcot-Marie-Tooth Disease 2w 75

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
highly variable age at onset (range childhood to late adult)
variable severity


HPO:

32
charcot-marie-tooth disease, axonal, type 2w:
Inheritance autosomal dominant inheritance
Onset and clinical course variable expressivity


Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

OMIM 57 616625
Disease Ontology 12 DOID:0110162
Orphanet 59 ORPHA488333
MeSH 44 D002607

Summaries for Charcot-Marie-Tooth Disease, Axonal, Type 2w

UniProtKB/Swiss-Prot : 75 Charcot-Marie-Tooth disease 2W: An autosomal dominant, axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2W patients manifest a peripheral neuropathy mainly affecting the lower limbs and resulting in gait difficulties and distal sensory impairment. Most patients also have upper limb involvement.

MalaCards based summary : Charcot-Marie-Tooth Disease, Axonal, Type 2w, also known as cmt2w, is related to perrault syndrome and retinitis pigmentosa. An important gene associated with Charcot-Marie-Tooth Disease, Axonal, Type 2w is HARS (Histidyl-TRNA Synthetase), and among its related pathways/superpathways is tRNA Aminoacylation. Related phenotypes are pes cavus and hammertoe

Disease Ontology : 12 A Charcot-Marie-Tooth disease type 2 that has material basis in heterozygous mutation in the HARS gene on chromosome 5q31.

OMIM : 57 Charcot-Marie-Tooth disease type 2W is an autosomal dominant neurologic disorder characterized by a peripheral neuropathy mainly affecting the lower limbs and resulting in gait difficulties and distal sensory impairment, although most patients also have upper limb involvement. The age at onset is highly variable, ranging from childhood to late adulthood (summary by Safka Brozkova et al., 2015). For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210). (616625)

Related Diseases for Charcot-Marie-Tooth Disease, Axonal, Type 2w

Symptoms & Phenotypes for Charcot-Marie-Tooth Disease, Axonal, Type 2w

Symptoms via clinical synopsis from OMIM:

57
Skeletal Feet:
pes cavus
hammertoes

Neurologic Peripheral Nervous System:
impaired gait
steppage gait
distal sensory impairment
brisk patellar reflexes
absent ankle reflexes
more
Muscle Soft Tissue:
distal muscle weakness of the lower limbs secondary to peripheral neuropathy
distal muscle atrophy of the lower limbs secondary to peripheral neuropathy
distal muscle weakness of the upper limbs (in some patients)
distal muscle atrophy of the upper limbs (in some patients)


Clinical features from OMIM:

616625

Human phenotypes related to Charcot-Marie-Tooth Disease, Axonal, Type 2w:

32
# Description HPO Frequency HPO Source Accession
1 pes cavus 32 HP:0001761
2 hammertoe 32 HP:0001765
3 steppage gait 32 HP:0003376
4 absent achilles reflex 32 HP:0003438
5 distal sensory impairment 32 HP:0002936

GenomeRNAi Phenotypes related to Charcot-Marie-Tooth Disease, Axonal, Type 2w according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-175 9.28 HARS
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-204 9.28 HARS
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-213 9.28 HARS
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-40 9.28 HARS HARS2
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-48 9.28 HARS
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-72 9.28 HARS2
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-94 9.28 HARS2
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-98 9.28 HARS

Drugs & Therapeutics for Charcot-Marie-Tooth Disease, Axonal, Type 2w

Search Clinical Trials , NIH Clinical Center for Charcot-Marie-Tooth Disease, Axonal, Type 2w

Genetic Tests for Charcot-Marie-Tooth Disease, Axonal, Type 2w

Genetic tests related to Charcot-Marie-Tooth Disease, Axonal, Type 2w:

# Genetic test Affiliating Genes
1 Charcot-Marie-Tooth Disease, Axonal, Type 2w 29 HARS

Anatomical Context for Charcot-Marie-Tooth Disease, Axonal, Type 2w

Publications for Charcot-Marie-Tooth Disease, Axonal, Type 2w

Variations for Charcot-Marie-Tooth Disease, Axonal, Type 2w

UniProtKB/Swiss-Prot genetic disease variations for Charcot-Marie-Tooth Disease, Axonal, Type 2w:

75
# Symbol AA change Variation ID SNP ID
1 HARS p.Arg137Gln VAR_069022 rs191391414
2 HARS p.Thr132Ile VAR_075064 rs143473232
3 HARS p.Pro134His VAR_075065 rs863225122
4 HARS p.Asp175Glu VAR_075066 rs863225123
5 HARS p.Asp364Tyr VAR_075067 rs863225124

ClinVar genetic disease variations for Charcot-Marie-Tooth Disease, Axonal, Type 2w:

6
(show all 14)
# Gene Variation Type Significance SNP ID Assembly Location
1 HARS NM_002109.5(HARS): c.395C> T (p.Thr132Ile) single nucleotide variant Pathogenic rs143473232 GRCh37 Chromosome 5, 140059374: 140059374
2 HARS NM_002109.5(HARS): c.395C> T (p.Thr132Ile) single nucleotide variant Pathogenic rs143473232 GRCh38 Chromosome 5, 140679789: 140679789
3 HARS NM_002109.5(HARS): c.401C> A (p.Pro134His) single nucleotide variant Pathogenic rs863225122 GRCh38 Chromosome 5, 140679123: 140679123
4 HARS NM_002109.5(HARS): c.401C> A (p.Pro134His) single nucleotide variant Pathogenic rs863225122 GRCh37 Chromosome 5, 140058708: 140058708
5 HARS NM_002109.5(HARS): c.525T> G (p.Asp175Glu) single nucleotide variant Pathogenic rs863225123 GRCh38 Chromosome 5, 140678013: 140678013
6 HARS NM_002109.5(HARS): c.525T> G (p.Asp175Glu) single nucleotide variant Pathogenic rs863225123 GRCh37 Chromosome 5, 140057598: 140057598
7 HARS NM_002109.5(HARS): c.1090G> T (p.Asp364Tyr) single nucleotide variant Pathogenic rs863225124 GRCh38 Chromosome 5, 140676758: 140676758
8 HARS NM_002109.5(HARS): c.1090G> T (p.Asp364Tyr) single nucleotide variant Pathogenic rs863225124 GRCh37 Chromosome 5, 140056343: 140056343
9 HARS NM_002109.5(HARS): c.464T> G (p.Val155Gly) single nucleotide variant Uncertain significance GRCh37 Chromosome 5, 140058645: 140058645
10 HARS NM_002109.5(HARS): c.464T> G (p.Val155Gly) single nucleotide variant Uncertain significance GRCh38 Chromosome 5, 140679060: 140679060
11 HARS NM_002109.5(HARS): c.989A> G (p.Tyr330Cys) single nucleotide variant Uncertain significance GRCh38 Chromosome 5, 140676859: 140676859
12 HARS NM_002109.5(HARS): c.989A> G (p.Tyr330Cys) single nucleotide variant Uncertain significance GRCh37 Chromosome 5, 140056444: 140056444
13 HARS NM_002109.5(HARS): c.1067G> A (p.Ser356Asn) single nucleotide variant Uncertain significance rs144322728 GRCh38 Chromosome 5, 140676781: 140676781
14 HARS NM_002109.5(HARS): c.1067G> A (p.Ser356Asn) single nucleotide variant Uncertain significance rs144322728 GRCh37 Chromosome 5, 140056366: 140056366

Expression for Charcot-Marie-Tooth Disease, Axonal, Type 2w

Search GEO for disease gene expression data for Charcot-Marie-Tooth Disease, Axonal, Type 2w.

Pathways for Charcot-Marie-Tooth Disease, Axonal, Type 2w

Pathways related to Charcot-Marie-Tooth Disease, Axonal, Type 2w according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
10.87 HARS HARS2

GO Terms for Charcot-Marie-Tooth Disease, Axonal, Type 2w

Biological processes related to Charcot-Marie-Tooth Disease, Axonal, Type 2w according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 translation GO:0006412 9.26 HARS HARS2
2 tRNA aminoacylation for protein translation GO:0006418 9.16 HARS HARS2
3 mitochondrial translation GO:0032543 8.96 HARS HARS2
4 histidyl-tRNA aminoacylation GO:0006427 8.62 HARS HARS2

Molecular functions related to Charcot-Marie-Tooth Disease, Axonal, Type 2w according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ligase activity GO:0016874 9.16 HARS HARS2
2 aminoacyl-tRNA ligase activity GO:0004812 8.96 HARS HARS2
3 histidine-tRNA ligase activity GO:0004821 8.62 HARS HARS2

Sources for Charcot-Marie-Tooth Disease, Axonal, Type 2w

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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