CMT2W
MCID: CHR544
MIFTS: 33

Charcot-Marie-Tooth Disease, Axonal, Type 2w (CMT2W)

Categories: Genetic diseases, Metabolic 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 58 76 30 6
Cmt2w 58 12 60 76
Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type 2w 58 76
Charcot-Marie-Tooth Disease, Axonal Type 2w 12 15
Charcot-Marie-Tooth Neuropathy, Type 2w 58 76
Autosomal Dominant Charcot-Marie-Tooth Disease Type 2 Due to Hars Mutation 60
Autosomal Dominant Axonal Charcot-Marie-Tooth Disease Type 2w 12
Autosomal Dominant Charcot-Marie-Tooth Disease Type 2w 60
Charcot-Marie-Tooth Neuropathy Type 2w 12
Charcot-Marie-Tooth Disease 2w 76

Characteristics:

OMIM:

58
Inheritance:
autosomal dominant

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


HPO:

33
charcot-marie-tooth disease, axonal, type 2w:
Onset and clinical course variable expressivity
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 60  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0110162
OMIM 58 616625
MeSH 45 D002607
Orphanet 60 ORPHA488333

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

UniProtKB/Swiss-Prot : 76 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 muscular disease. 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. Affiliated tissues include bone and skin, and related phenotypes are impaired vibration sensation in the lower limbs and distal lower limb muscle weakness

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 : 58 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

Diseases in the Charcot-Marie-Tooth Disease, Axonal, Type 2e family:

Charcot-Marie-Tooth Disease, Axonal, Type 2a1 Charcot-Marie-Tooth Disease, Axonal, Type 2b
Charcot-Marie-Tooth Disease, Axonal, Type 2d Charcot-Marie-Tooth Disease, Axonal, Type 2b1
Charcot-Marie-Tooth Disease, Axonal, Type 2b2 Charcot-Marie-Tooth Disease, Axonal, Type 2f
Charcot-Marie-Tooth Disease, Axonal, Type 2i Charcot-Marie-Tooth Disease, Axonal, Type 2h
Charcot-Marie-Tooth Disease, Axonal, Type 2j Charcot-Marie-Tooth Disease, Axonal, Type 2k
Charcot-Marie-Tooth Disease, Axonal, Type 2l Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type 2a2a
Charcot-Marie-Tooth Disease, Axonal, Type 2n Charcot-Marie-Tooth Disease, Axonal, Type 2o
Charcot-Marie-Tooth Disease, Axonal, Type 2p Charcot-Marie-Tooth Disease, Axonal, Type 2q
Charcot-Marie-Tooth Disease, Axonal, Type 2r Charcot-Marie-Tooth Disease, Axonal, Type 2u
Charcot-Marie-Tooth Disease, Axonal, Type 2v Charcot-Marie-Tooth Disease, Axonal, Type 2w
Charcot-Marie-Tooth Disease, Axonal, Type 2x Charcot-Marie-Tooth Disease, Axonal, Type 2z
Charcot-Marie-Tooth Disease, Axonal, Type 2cc Charcot-Marie-Tooth Disease, Axonal, Type 2t
Charcot-Marie-Tooth Disease, Axonal, Autosomal Recessive, Type 2a2b Charcot-Marie-Tooth Disease, Axonal, Type 2dd
Charcot-Marie-Tooth Disease, Axonal, Type 2ee Autosomal Recessive Axonal Charcot-Marie-Tooth Disease Due to Copper Metabolism Defect

Diseases related to Charcot-Marie-Tooth Disease, Axonal, Type 2w via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 perrault syndrome 9.7 HARS HARS2
2 muscular disease 9.6 HARS HARS2
3 retinitis pigmentosa 9.5 HARS HARS2

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

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

60 33 (show all 21)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 impaired vibration sensation in the lower limbs 60 33 hallmark (90%) Very frequent (99-80%) HP:0002166
2 distal lower limb muscle weakness 60 33 hallmark (90%) Very frequent (99-80%) HP:0009053
3 distal upper limb muscle weakness 60 33 hallmark (90%) Very frequent (99-80%) HP:0008959
4 demyelinating peripheral neuropathy 60 33 hallmark (90%) Very frequent (99-80%) HP:0007108
5 pes cavus 60 33 frequent (33%) Frequent (79-30%) HP:0001761
6 brisk reflexes 60 33 frequent (33%) Frequent (79-30%) HP:0001348
7 steppage gait 60 33 frequent (33%) Frequent (79-30%) HP:0003376
8 motor axonal neuropathy 60 33 frequent (33%) Frequent (79-30%) HP:0007002
9 pain 60 33 occasional (7.5%) Occasional (29-5%) HP:0012531
10 impaired pain sensation 60 33 occasional (7.5%) Occasional (29-5%) HP:0007328
11 hammertoe 60 33 occasional (7.5%) Occasional (29-5%) HP:0001765
12 absent achilles reflex 60 33 occasional (7.5%) Occasional (29-5%) HP:0003438
13 intrinsic hand muscle atrophy 60 33 occasional (7.5%) Occasional (29-5%) HP:0008954
14 slender long bone 60 33 occasional (7.5%) Occasional (29-5%) HP:0003100
15 hand muscle weakness 60 33 occasional (7.5%) Occasional (29-5%) HP:0030237
16 tip-toe gait 60 33 occasional (7.5%) Occasional (29-5%) HP:0030051
17 impaired distal tactile sensation 60 33 occasional (7.5%) Occasional (29-5%) HP:0006937
18 gait disturbance 60 Frequent (79-30%)
19 abnormality of the foot 60 Frequent (79-30%)
20 sensory impairment 60 Very frequent (99-80%)
21 distal sensory impairment 33 HP:0002936

Symptoms via clinical synopsis from OMIM:

58
Skeletal Feet:
pes cavus
hammertoes

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)

Neurologic Peripheral Nervous System:
steppage gait
distal sensory impairment
impaired gait
absent ankle reflexes
brisk patellar reflexes
more

Clinical features from OMIM:

616625

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

27
# 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 30 HARS

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

MalaCards organs/tissues related to Charcot-Marie-Tooth Disease, Axonal, Type 2w:

42
Bone, Skin

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

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

# Title Authors Year
1
Loss of function mutations in HARS cause a spectrum of inherited peripheral neuropathies. ( 26072516 )
2015
2
A loss-of-function variant in the human histidyl-tRNA synthetase (HARS) gene is neurotoxic in vivo. ( 22930593 )
2013

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

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

76
# 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 20)
# Gene Variation Type Significance SNP ID Assembly Location
1 HARS NM_002109.5(HARS): c.410G> A (p.Arg137Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs191391414 GRCh37 Chromosome 5, 140058699: 140058699
2 HARS NM_002109.5(HARS): c.410G> A (p.Arg137Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs191391414 GRCh38 Chromosome 5, 140679114: 140679114
3 HARS NM_002109.5(HARS): c.395C> T (p.Thr132Ile) single nucleotide variant Pathogenic rs143473232 GRCh37 Chromosome 5, 140059374: 140059374
4 HARS NM_002109.5(HARS): c.395C> T (p.Thr132Ile) single nucleotide variant Pathogenic rs143473232 GRCh38 Chromosome 5, 140679789: 140679789
5 HARS NM_002109.5(HARS): c.401C> A (p.Pro134His) single nucleotide variant Pathogenic rs863225122 GRCh38 Chromosome 5, 140679123: 140679123
6 HARS NM_002109.5(HARS): c.401C> A (p.Pro134His) single nucleotide variant Pathogenic rs863225122 GRCh37 Chromosome 5, 140058708: 140058708
7 HARS NM_002109.5(HARS): c.525T> G (p.Asp175Glu) single nucleotide variant Pathogenic rs863225123 GRCh38 Chromosome 5, 140678013: 140678013
8 HARS NM_002109.5(HARS): c.525T> G (p.Asp175Glu) single nucleotide variant Pathogenic rs863225123 GRCh37 Chromosome 5, 140057598: 140057598
9 HARS NM_002109.5(HARS): c.1090G> T (p.Asp364Tyr) single nucleotide variant Pathogenic rs863225124 GRCh38 Chromosome 5, 140676758: 140676758
10 HARS NM_002109.5(HARS): c.1090G> T (p.Asp364Tyr) single nucleotide variant Pathogenic rs863225124 GRCh37 Chromosome 5, 140056343: 140056343
11 HARS NM_002109.5(HARS): c.464T> G (p.Val155Gly) single nucleotide variant Uncertain significance rs1239341211 GRCh37 Chromosome 5, 140058645: 140058645
12 HARS NM_002109.5(HARS): c.464T> G (p.Val155Gly) single nucleotide variant Uncertain significance rs1239341211 GRCh38 Chromosome 5, 140679060: 140679060
13 HARS NM_002109.5(HARS): c.989A> G (p.Tyr330Cys) single nucleotide variant Uncertain significance rs1554106881 GRCh38 Chromosome 5, 140676859: 140676859
14 HARS NM_002109.5(HARS): c.989A> G (p.Tyr330Cys) single nucleotide variant Uncertain significance rs1554106881 GRCh37 Chromosome 5, 140056444: 140056444
15 HARS NM_002109.5(HARS): c.1067G> A (p.Ser356Asn) single nucleotide variant Uncertain significance rs144322728 GRCh37 Chromosome 5, 140056366: 140056366
16 HARS NM_002109.5(HARS): c.1067G> A (p.Ser356Asn) single nucleotide variant Uncertain significance rs144322728 GRCh38 Chromosome 5, 140676781: 140676781
17 HARS NM_002109.5(HARS): c.90+1G> C single nucleotide variant Likely pathogenic rs1554109203 GRCh37 Chromosome 5, 140070799: 140070799
18 HARS NM_002109.5(HARS): c.90+1G> C single nucleotide variant Likely pathogenic rs1554109203 GRCh38 Chromosome 5, 140691214: 140691214
19 HARS NM_002109.5(HARS): c.397G> T (p.Val133Phe) single nucleotide variant Likely pathogenic rs1554107200 GRCh37 Chromosome 5, 140058712: 140058712
20 HARS NM_002109.5(HARS): c.397G> T (p.Val133Phe) single nucleotide variant Likely pathogenic rs1554107200 GRCh38 Chromosome 5, 140679127: 140679127

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 9.16 HARS HARS2
2 tRNA aminoacylation for protein translation GO:0006418 8.96 HARS HARS2
3 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 identical protein binding GO:0042802 9.26 HARS HARS2
2 ligase activity GO:0016874 9.16 HARS HARS2
3 aminoacyl-tRNA ligase activity GO:0004812 8.96 HARS HARS2
4 histidine-tRNA ligase activity GO:0004821 8.62 HARS HARS2

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

3 CDC
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9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
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35 ICD10 via Orphanet
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46 MESH via Orphanet
47 MGI
50 NCI
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58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
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75 UMLS via Orphanet
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