CMT2A1
MCID: CHR626
MIFTS: 39

Charcot-Marie-Tooth Disease, Axonal, Type 2a1 (CMT2A1)

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

Aliases & Classifications for Charcot-Marie-Tooth Disease, Axonal, Type 2a1

MalaCards integrated aliases for Charcot-Marie-Tooth Disease, Axonal, Type 2a1:

Name: Charcot-Marie-Tooth Disease, Axonal, Type 2a1 56 71
Charcot-Marie-Tooth Disease, Type 2a1 56 29 13 6 39
Cmt2a1 56 12 58 73
Hereditary Motor and Sensory Neuropathy Iia1 56 12 73
Hmsn Iia1 56 12 73
Hmsn2a1 56 12 73
Charcot-Marie-Tooth Disease Neuronal Type 2a1 12 73
Charcot-Marie-Tooth Neuropathy Type 2a1 12 73
Charcot-Marie-Tooth Disease Type 2a1 12 15
Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type 2a1 56
Autosomal Dominant Charcot-Marie-Tooth Disease Axonal Type 2a1 12
Autosomal Dominant Charcot-Marie-Tooth Disease Type 2a1 58
Charcot-Marie-Tooth Disease, Neuronal, Type 2a1 56
Charcot-Marie-Tooth Disease Axonal Type 2a1 73
Charcot-Marie-Tooth Neuropathy, Type 2a1 56
Charcot-Marie-Tooth Disease 2a1 73

Characteristics:

Orphanet epidemiological data:

58
autosomal dominant charcot-marie-tooth disease type 2a1
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
slowly progressive
usually begins in feet and legs (peroneal distribution)
peak age of onset in second decade (range childhood to 50 years)
may progress to upper limbs
genetic heterogeneity (see cmt2a2 )
for autosomal recessive forms, see cmt2b1


HPO:

31
charcot-marie-tooth disease, axonal, type 2a1:
Inheritance autosomal dominant inheritance heterogeneous
Onset and clinical course onset slow progression


Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0110154
OMIM 56 118210
OMIM Phenotypic Series 56 PS118220
ICD10 32 G60.0
ICD10 via Orphanet 33 G60.0
UMLS via Orphanet 72 C1861678
Orphanet 58 ORPHA99946
MedGen 41 C1861678
UMLS 71 C1861678

Summaries for Charcot-Marie-Tooth Disease, Axonal, Type 2a1

OMIM : 56 Charcot-Marie-Tooth disease constitutes a clinically and genetically heterogeneous group of hereditary motor and sensory neuropathies. On the basis of electrophysiologic criteria, CMT is divided into 2 major types: type 1, the demyelinating form, characterized by a slow motor median nerve conduction velocity (NCV) (less than 38 m/s), and type 2, the axonal form, with a normal or slightly reduced NCV. Distal hereditary motor neuropathy (dHMN), also known as spinal CMT, is a third type of CMT characterized by normal motor and sensory NCV and degeneration of spinal cord anterior horn cells. See CMT1B (118200) and CMT1A (118220) for descriptions of autosomal dominant slow nerve conduction types of Charcot-Marie-Tooth disease. See CMT4A (214400) and CMTX1 (302800) for autosomal recessive and X-linked forms of Charcot-Marie-Tooth disease, respectively. (118210)

MalaCards based summary : Charcot-Marie-Tooth Disease, Axonal, Type 2a1, also known as charcot-marie-tooth disease, type 2a1, is related to charcot-marie-tooth disease, axonal, type 2t and charcot-marie-tooth disease, axonal, type 2b1. An important gene associated with Charcot-Marie-Tooth Disease, Axonal, Type 2a1 is KIF1B (Kinesin Family Member 1B), and among its related pathways/superpathways is NgR-p75(NTR)-Mediated Signaling. Affiliated tissues include spinal cord and skin, and related phenotypes are areflexia and peripheral neuropathy

Disease Ontology : 12 A Charcot-Marie-Tooth disease type 2 that has material basis in heterozygous mutation in the KIF1B gene on chromosome 1p36.

UniProtKB/Swiss-Prot : 73 Charcot-Marie-Tooth disease 2A1: A 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.

Related Diseases for Charcot-Marie-Tooth Disease, Axonal, Type 2a1

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 2a1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 73)
# Related Disease Score Top Affiliating Genes
1 charcot-marie-tooth disease, axonal, type 2t 31.4 LRSAM1 GDAP1
2 charcot-marie-tooth disease, axonal, type 2b1 31.2 MFN2 LRSAM1 GDAP1
3 charcot-marie-tooth disease, axonal, type 2j 30.9 MPZ MFN2 KIF1B GDAP1
4 charcot-marie-tooth disease, x-linked dominant, 1 30.9 MPZ MFN2 KIF1B GDAP1
5 charcot-marie-tooth disease, axonal, type 2b2 30.4 MPZ MFN2 LRSAM1 KIF1B GDAP1
6 neuromyotonia and axonal neuropathy, autosomal recessive 11.1
7 hereditary motor and sensory neuropathy v 11.1
8 neuropathy, hereditary, with or without age-related macular degeneration 11.1
9 charcot-marie-tooth disease, axonal, type 2u 11.1
10 charcot-marie-tooth disease, axonal, type 2w 11.1
11 charcot-marie-tooth disease, axonal, type 2x 11.1
12 charcot-marie-tooth disease, axonal, type 2z 11.1
13 charcot-marie-tooth disease type 2a 10.3 MFN2 KIF1B
14 charcot-marie-tooth neuropathy type 2a 10.2 MFN2 KIF1B
15 charcot-marie-tooth disease, dominant intermediate d 10.2 MPZ KIF1B
16 hereditary neuropathies 10.1 MPZ MFN2
17 adie pupil 10.1 MPZ ARHGEF10
18 charcot-marie-tooth disease, axonal, type 2cc 10.1 MPZ MFN2
19 charcot-marie-tooth disease, x-linked recessive, 2 10.1 MPZ DYNC1H1
20 argyll robertson pupil 10.0 MPZ GDAP1
21 abnormal pupillary function 10.0 MPZ GDAP1
22 pupil disease 10.0 MPZ GDAP1
23 charcot-marie-tooth disease, dominant intermediate a 10.0 MPZ GDAP1
24 mononeuropathy 10.0 MPZ ARHGEF10
25 charcot-marie-tooth disease, recessive intermediate a 10.0 MFN2 GDAP1
26 charcot-marie-tooth disease, demyelinating, type 4f 9.9 MPZ GDAP1
27 charcot-marie-tooth disease, axonal, type 2h 9.9 LRSAM1 GDAP1
28 charcot-marie-tooth disease, dominant intermediate b 9.9 MPZ GDAP1
29 charcot-marie-tooth disease, axonal, type 2r 9.9 LRSAM1 GDAP1
30 nerve compression syndrome 9.9 MPZ ARHGEF10
31 spastic paraplegia 55, autosomal recessive 9.9 LRSAM1 GDAP1
32 charcot-marie-tooth disease, type 4b2 9.9 MPZ GDAP1
33 charcot-marie-tooth disease, axonal, type 2q 9.9 MPZ DYNC1H1
34 charcot-marie-tooth disease, axonal, type 2k 9.9 GDAP1 DYNC1H1
35 charcot-marie-tooth disease, type 4d 9.8 MPZ GDAP1
36 charcot-marie-tooth disease, demyelinating, type 1d 9.8 MPZ KIF1B GDAP1
37 charcot-marie-tooth disease, demyelinating, type 1f 9.8 MPZ LRSAM1 DYNC1H1
38 charcot-marie-tooth disease, type 4b1 9.7 MPZ GDAP1
39 polyneuropathy 9.7 MPZ MFN2 GDAP1
40 charcot-marie-tooth disease, dominant intermediate e 9.7 MPZ GDAP1 DYNC1H1
41 charcot-marie-tooth disease, type 4h 9.6 MPZ GDAP1 ARHGEF10
42 neuropathy, hereditary sensory and autonomic, type iia 9.6 MFN2 GDAP1
43 charcot-marie-tooth disease, axonal, type 2p 9.6 LRSAM1 GDAP1 ARHGEF10
44 charcot-marie-tooth disease, axonal, type 2b 9.5 MPZ MFN2 KIF1B GDAP1
45 motor peripheral neuropathy 9.5 GDAP1 DYNC1H1 ARHGEF10
46 charcot-marie-tooth disease type 2a2a 9.5 MPZ MFN2 KIF1B GDAP1
47 charcot-marie-tooth disease, axonal, type 2l 9.5 MPZ MFN2 KIF1B GDAP1
48 charcot-marie-tooth disease, axonal, type 2i 9.5 MPZ MFN2 KIF1B GDAP1
49 charcot-marie-tooth disease, axonal, type 2f 9.5 MPZ MFN2 KIF1B GDAP1
50 charcot-marie-tooth disease type x 9.5 MPZ MFN2 KIF1B GDAP1

Graphical network of the top 20 diseases related to Charcot-Marie-Tooth Disease, Axonal, Type 2a1:



Diseases related to Charcot-Marie-Tooth Disease, Axonal, Type 2a1

Symptoms & Phenotypes for Charcot-Marie-Tooth Disease, Axonal, Type 2a1

Human phenotypes related to Charcot-Marie-Tooth Disease, Axonal, Type 2a1:

31 (show all 16)
# Description HPO Frequency HPO Source Accession
1 areflexia 31 HP:0001284
2 peripheral neuropathy 31 HP:0009830
3 pes cavus 31 HP:0001761
4 decreased motor nerve conduction velocity 31 HP:0003431
5 hyporeflexia 31 HP:0001265
6 distal amyotrophy 31 HP:0003693
7 foot dorsiflexor weakness 31 HP:0009027
8 limb muscle weakness 31 HP:0003690
9 hammertoe 31 HP:0001765
10 distal muscle weakness 31 HP:0002460
11 steppage gait 31 HP:0003376
12 distal sensory impairment 31 HP:0002936
13 decreased number of peripheral myelinated nerve fibers 31 HP:0003380
14 onion bulb formation 31 HP:0003383
15 axonal degeneration/regeneration 31 HP:0003378
16 peripheral axonal atrophy 31 HP:0003384

Symptoms via clinical synopsis from OMIM:

56
Neurologic Peripheral Nervous System:
areflexia
hyporeflexia
distal limb muscle weakness due to peripheral neuropathy
distal limb muscle atrophy due to peripheral neuropathy
'steppage' gait
more
Skeletal Feet:
pes cavus
foot deformities
hammer toes

Clinical features from OMIM:

118210

MGI Mouse Phenotypes related to Charcot-Marie-Tooth Disease, Axonal, Type 2a1:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.56 AARS1 ARHGEF10 DYNC1H1 GDAP1 KIF1B LRSAM1
2 nervous system MP:0003631 9.23 AARS1 ARHGEF10 DYNC1H1 GDAP1 KIF1B LRSAM1

Drugs & Therapeutics for Charcot-Marie-Tooth Disease, Axonal, Type 2a1

Search Clinical Trials , NIH Clinical Center for Charcot-Marie-Tooth Disease, Axonal, Type 2a1

Genetic Tests for Charcot-Marie-Tooth Disease, Axonal, Type 2a1

Genetic tests related to Charcot-Marie-Tooth Disease, Axonal, Type 2a1:

# Genetic test Affiliating Genes
1 Charcot-Marie-Tooth Disease, Type 2a1 29 KIF1B

Anatomical Context for Charcot-Marie-Tooth Disease, Axonal, Type 2a1

MalaCards organs/tissues related to Charcot-Marie-Tooth Disease, Axonal, Type 2a1:

40
Spinal Cord, Skin

Publications for Charcot-Marie-Tooth Disease, Axonal, Type 2a1

Articles related to Charcot-Marie-Tooth Disease, Axonal, Type 2a1:

# Title Authors PMID Year
1
Charcot-Marie-Tooth disease type 2A caused by mutation in a microtubule motor KIF1Bbeta. 56 6
11389829 2001
2
Linkage mapping of the gene for Charcot-Marie-Tooth disease type 2 to chromosome 1p (CMT2A) and the clinical features of CMT2A. 56 6
9409358 1997
3
Charcot-Marie-Tooth Neuropathy Type 2A 6
20301684 2005
4
Charcot-Marie-Tooth (CMT) Hereditary Neuropathy Overview 6
20301532 1998
5
Charcot-Marie-Tooth Neuropathy Type 2 6
20301462 1998
6
Localization of a gene (CMT2A) for autosomal dominant Charcot-Marie-Tooth disease type 2 to chromosome 1p and evidence of genetic heterogeneity. 56
8406488 1993
7
Clinical and genetic heterogeneity of Charcot-Marie-Tooth disease. 56
1733853 1992
8
A novel founder mutation in the MFN2 gene associated with variable Charcot-Marie-Tooth type 2 phenotype in two families from Southern Italy. 61
21686698 2009

Variations for Charcot-Marie-Tooth Disease, Axonal, Type 2a1

ClinVar genetic disease variations for Charcot-Marie-Tooth Disease, Axonal, Type 2a1:

6 ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 KIF1B NM_015074.3(KIF1B):c.293A>T (p.Gln98Leu)SNV Pathogenic 4658 rs121908160 1:10318660-10318660 1:10258602-10258602
2 KIF1B NM_015074.3(KIF1B):c.1567A>G (p.Ile523Val)SNV Uncertain significance 408309 rs374848403 1:10355752-10355752 1:10295694-10295694
3 KIF1B NM_015074.3(KIF1B):c.2021C>T (p.Thr674Ile)SNV Uncertain significance 408312 rs41274468 1:10380144-10380144 1:10320086-10320086

UniProtKB/Swiss-Prot genetic disease variations for Charcot-Marie-Tooth Disease, Axonal, Type 2a1:

73
# Symbol AA change Variation ID SNP ID
1 KIF1B p.Gln98Leu VAR_011515 rs121908160

Expression for Charcot-Marie-Tooth Disease, Axonal, Type 2a1

Search GEO for disease gene expression data for Charcot-Marie-Tooth Disease, Axonal, Type 2a1.

Pathways for Charcot-Marie-Tooth Disease, Axonal, Type 2a1

Pathways related to Charcot-Marie-Tooth Disease, Axonal, Type 2a1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.29 GDAP1 ARHGEF10

GO Terms for Charcot-Marie-Tooth Disease, Axonal, Type 2a1

Cellular components related to Charcot-Marie-Tooth Disease, Axonal, Type 2a1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 axon cytoplasm GO:1904115 8.62 KIF1B DYNC1H1

Biological processes related to Charcot-Marie-Tooth Disease, Axonal, Type 2a1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 microtubule-based movement GO:0007018 9.16 KIF1B DYNC1H1
2 protein targeting to mitochondrion GO:0006626 8.96 MFN2 GDAP1
3 mitochondrial fusion GO:0008053 8.62 MFN2 GDAP1

Molecular functions related to Charcot-Marie-Tooth Disease, Axonal, Type 2a1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 microtubule motor activity GO:0003777 8.96 KIF1B DYNC1H1
2 kinesin binding GO:0019894 8.62 KIF1B ARHGEF10

Sources for Charcot-Marie-Tooth Disease, Axonal, Type 2a1

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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