CMT2W
MCID: CHR544
MIFTS: 34

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

Categories: Ear diseases, Genetic diseases, Metabolic diseases, Muscle 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 72 29 6
Cmt2w 57 12 58 72
Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type 2w 57 72
Charcot-Marie-Tooth Disease, Axonal Type 2w 12 15
Charcot-Marie-Tooth Neuropathy, Type 2w 57 72
Autosomal Dominant Charcot-Marie-Tooth Disease Type 2 Due to Hars Mutation 58
Autosomal Dominant Axonal Charcot-Marie-Tooth Disease Type 2w 12
Autosomal Dominant Charcot-Marie-Tooth Disease Type 2w 58
Charcot-Marie-Tooth Neuropathy Type 2w 12
Charcot-Marie-Tooth Disease 2w 72

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal dominant

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


HPO:

31
charcot-marie-tooth disease, axonal, type 2w:
Inheritance autosomal dominant inheritance
Onset and clinical course variable expressivity


Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0110162
OMIM® 57 616625
OMIM Phenotypic Series 57 PS118220
MeSH 44 D002607
Orphanet 58 ORPHA488333

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

UniProtKB/Swiss-Prot : 72 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 slowed nerve conduction velocity, autosomal dominant and charcot-marie-tooth disease, x-linked recessive, 2. An important gene associated with Charcot-Marie-Tooth Disease, Axonal, Type 2w is HARS1 (Histidyl-TRNA Synthetase 1), and among its related pathways/superpathways is Neural Crest Differentiation. Affiliated tissues include bone, and related phenotypes are distal lower limb muscle weakness and demyelinating peripheral neuropathy

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) (Updated 20-May-2021)

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:

(show top 50) (show all 56)
# Related Disease Score Top Affiliating Genes
1 slowed nerve conduction velocity, autosomal dominant 9.8 MPZ GJB1
2 charcot-marie-tooth disease, x-linked recessive, 2 9.8 MPZ GJB1
3 autoimmune peripheral neuropathy 9.8 MPZ GJB1
4 hereditary neuropathies 9.8 MPZ GJB1
5 brachial plexus neuropathy 9.8 MPZ GJB1
6 pupil disease 9.8 MPZ GDAP1
7 argyll robertson pupil 9.8 MPZ GDAP1
8 abnormal pupillary function 9.8 MPZ GDAP1
9 charcot-marie-tooth disease, axonal, type 2a1 9.8 MPZ GDAP1
10 charcot-marie-tooth disease, dominant intermediate e 9.8 MPZ GDAP1
11 charcot-marie-tooth disease, axonal, type 2j 9.8 MPZ GDAP1
12 charcot-marie-tooth disease x-linked recessive 4 9.8 MPZ GJB1
13 charcot-marie-tooth disease, axonal, type 2l 9.8 MPZ GDAP1
14 charcot-marie-tooth disease, type 4b3 9.7 MPZ GDAP1
15 charcot-marie-tooth disease, demyelinating, type 4f 9.7 MPZ GDAP1
16 charcot-marie-tooth disease, dominant intermediate b 9.7 MPZ GDAP1
17 charcot-marie-tooth disease, type 4h 9.7 MPZ GDAP1
18 charcot-marie-tooth disease, type 4j 9.7 MPZ GDAP1
19 peripheral demyelinating neuropathy, central dysmyelination, waardenburg syndrome, and hirschsprung disease 9.7 MPZ GJB1
20 charcot-marie-tooth disease, axonal, type 2b2 9.7 MPZ GDAP1
21 charcot-marie-tooth disease, type 4b1 9.6 MPZ GDAP1
22 waardenburg syndrome, type 4a 9.6 MPZ GJB1
23 neuronopathy, distal hereditary motor, type va 9.6 HARS1 GDAP1
24 tremor 9.6 MPZ HARS1
25 neuritis 9.6 MPZ HARS1 GJB1
26 charcot-marie-tooth disease, dominant intermediate a 9.5 MPZ GJB1 GDAP1
27 charcot-marie-tooth disease, axonal, type 2i 9.5 MPZ GJB1 GDAP1
28 charcot-marie-tooth disease, demyelinating, type 1d 9.5 MPZ GJB1 GDAP1
29 charcot-marie-tooth disease intermediate type 9.5 MPZ GJB1 GDAP1
30 charcot-marie-tooth disease type x 9.5 MPZ GJB1 GDAP1
31 charcot-marie-tooth disease, dominant intermediate c 9.5 MPZ GJB1 GDAP1
32 charcot-marie-tooth disease, demyelinating, type 1f 9.5 MPZ GJB1 GDAP1
33 hereditary motor and sensory neuropathy, type iic 9.5 MPZ GJB1 GDAP1
34 charcot-marie-tooth disease, axonal, type 2f 9.5 MPZ GJB1 GDAP1
35 charcot-marie-tooth disease, x-linked dominant, 1 9.5 MPZ GJB1 GDAP1
36 charcot-marie-tooth disease, type 4a 9.5 MPZ GJB1 GDAP1
37 charcot-marie-tooth disease, axonal, type 2d 9.5 MPZ GJB1 GDAP1
38 charcot-marie-tooth disease, type 4d 9.5 MPZ GJB1 GDAP1
39 charcot-marie-tooth disease, axonal, type 2b 9.5 MPZ GJB1 GDAP1
40 charcot-marie-tooth disease, demyelinating, type 1b 9.5 MPZ GJB1 GDAP1
41 charcot-marie-tooth disease, type 4c 9.5 MPZ GJB1 GDAP1
42 neuropathy, hereditary, with liability to pressure palsies 9.5 MPZ GJB1 GDAP1
43 charcot-marie-tooth disease, demyelinating, type 1a 9.5 MPZ GJB1 GDAP1
44 charcot-marie-tooth disease, demyelinating, type 1c 9.5 MPZ GJB1 GDAP1
45 charcot-marie-tooth disease, type 4b2 9.5 MPZ GJB1 GDAP1
46 hypertrophic neuropathy of dejerine-sottas 9.5 MPZ GJB1 GDAP1
47 sensory peripheral neuropathy 9.5 MPZ GJB1 GDAP1
48 charcot-marie-tooth disease and deafness 9.5 MPZ GJB1 GDAP1
49 polyneuropathy 9.5 MPZ GJB1 GDAP1
50 neuropathy, congenital hypomyelinating, 1, autosomal recessive 9.4 MPZ GJB1 GDAP1

Graphical network of the top 20 diseases related to Charcot-Marie-Tooth Disease, Axonal, Type 2w:



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

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

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

58 31 (show all 25)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 distal lower limb muscle weakness 58 31 hallmark (90%) Very frequent (99-80%) HP:0009053
2 demyelinating peripheral neuropathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0007108
3 distal upper limb muscle weakness 58 31 hallmark (90%) Very frequent (99-80%) HP:0008959
4 impaired vibration sensation in the lower limbs 58 31 hallmark (90%) Very frequent (99-80%) HP:0002166
5 pes cavus 58 31 frequent (33%) Frequent (79-30%) HP:0001761
6 steppage gait 58 31 frequent (33%) Frequent (79-30%) HP:0003376
7 motor axonal neuropathy 58 31 frequent (33%) Frequent (79-30%) HP:0007002
8 brisk reflexes 58 31 frequent (33%) Frequent (79-30%) HP:0001348
9 slender long bone 58 31 occasional (7.5%) Occasional (29-5%) HP:0003100
10 impaired pain sensation 58 31 occasional (7.5%) Occasional (29-5%) HP:0007328
11 hammertoe 58 31 occasional (7.5%) Occasional (29-5%) HP:0001765
12 intrinsic hand muscle atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0008954
13 pain 58 31 occasional (7.5%) Occasional (29-5%) HP:0012531
14 hand muscle weakness 58 31 occasional (7.5%) Occasional (29-5%) HP:0030237
15 absent achilles reflex 58 31 occasional (7.5%) Occasional (29-5%) HP:0003438
16 tip-toe gait 58 31 occasional (7.5%) Occasional (29-5%) HP:0030051
17 impaired distal tactile sensation 58 31 occasional (7.5%) Occasional (29-5%) HP:0006937
18 gait disturbance 58 Frequent (79-30%)
19 abnormality of the foot 58 Frequent (79-30%)
20 peripheral neuropathy 31 HP:0009830
21 sensory impairment 58 Very frequent (99-80%)
22 distal muscle weakness 31 HP:0002460
23 distal sensory impairment 31 HP:0002936
24 distal amyotrophy 31 HP:0003693
25 hyperactive patellar reflex 31 HP:0007083

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
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 (Updated 20-May-2021)

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-143 9.23 GJB1
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-163 9.23 GJB1
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-175 9.23 HARS1
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-185 9.23 GJB1
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-29 9.23 HARS1
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-40 9.23 HARS1
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-49 9.23 GJB1
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-54 9.23 HARS1

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 HARS1

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

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

40
Bone

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

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

# Title Authors PMID Year
1
Loss of function mutations in HARS cause a spectrum of inherited peripheral neuropathies. 6 57
26072516 2015
2
A loss-of-function variant in the human histidyl-tRNA synthetase (HARS) gene is neurotoxic in vivo. 6 57
22930593 2013
3
Diagnostic yield of targeted sequential and massive panel approaches for inherited neuropathies. 61
32506583 2020
4
Substrate interaction defects in histidyl-tRNA synthetase linked to dominant axonal peripheral neuropathy. 61
29235198 2018

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

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

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 HARS1 NM_002109.6(HARS1):c.401C>A (p.Pro134His) SNV Pathogenic 217507 rs863225122 GRCh37: 5:140058708-140058708
GRCh38: 5:140679123-140679123
2 HARS1 NM_002109.6(HARS1):c.525T>G (p.Asp175Glu) SNV Pathogenic 217508 rs863225123 GRCh37: 5:140057598-140057598
GRCh38: 5:140678013-140678013
3 HARS1 NM_002109.6(HARS1):c.1090G>T (p.Asp364Tyr) SNV Pathogenic 217509 rs863225124 GRCh37: 5:140056343-140056343
GRCh38: 5:140676758-140676758
4 HARS1 NM_002109.6(HARS1):c.410G>A (p.Arg137Gln) SNV Pathogenic 40062 rs191391414 GRCh37: 5:140058699-140058699
GRCh38: 5:140679114-140679114
5 HARS1 NM_002109.6(HARS1):c.395C>T (p.Thr132Ile) SNV Pathogenic 217506 rs143473232 GRCh37: 5:140059374-140059374
GRCh38: 5:140679789-140679789
6 HARS1 NM_002109.6(HARS1):c.90+1G>C SNV Likely pathogenic 546982 rs1554109203 GRCh37: 5:140070799-140070799
GRCh38: 5:140691214-140691214
7 HARS1 NM_002109.6(HARS1):c.397G>T (p.Val133Phe) SNV Likely pathogenic 548118 rs1554107200 GRCh37: 5:140058712-140058712
GRCh38: 5:140679127-140679127
8 HARS1 NM_002109.6(HARS1):c.1067G>A (p.Ser356Asn) SNV Uncertain significance 446301 rs144322728 GRCh37: 5:140056366-140056366
GRCh38: 5:140676781-140676781
9 HARS1 NM_002109.6(HARS1):c.989A>G (p.Tyr330Cys) SNV Uncertain significance 446300 rs1554106881 GRCh37: 5:140056444-140056444
GRCh38: 5:140676859-140676859
10 HARS1 NM_002109.6(HARS1):c.464T>G (p.Val155Gly) SNV Uncertain significance 446299 rs1239341211 GRCh37: 5:140058645-140058645
GRCh38: 5:140679060-140679060

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

72
# Symbol AA change Variation ID SNP ID
1 HARS1 p.Arg137Gln VAR_069022 rs191391414
2 HARS1 p.Thr132Ile VAR_075064 rs143473232
3 HARS1 p.Pro134His VAR_075065 rs863225122
4 HARS1 p.Asp175Glu VAR_075066 rs863225123
5 HARS1 p.Asp364Tyr VAR_075067 rs863225124
6 HARS1 p.Tyr330Cys VAR_083004 rs155410688

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 10.63 MPZ GJB1

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

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

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