MCID: CHR350
MIFTS: 38

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

Categories: Genetic diseases, Rare diseases, Neuronal diseases

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

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

Name: Charcot-Marie-Tooth Disease, Axonal, Type 2k 54 13 69
Autosomal Recessive Charcot-Marie-Tooth Disease with Hoarseness 12 50 56
Autosomal Recessive Axonal Charcot-Marie-Tooth Disease Type 2k 12 50 56
Charcot-Marie-Tooth Disease Axonal Type 2k 12 71 14
Autosomal Recessive Axonal Cmt4c4 12 50 56
Arcmt2k 12 50 56
Cmt2k 56 71
Charcot-Marie-Tooth Neuropathy, Axonal, with Vocal Cord Paresis, Autosomal Recessive 50
Autosomal Recessive Axonal Charcot-Marie-Tooth Disease Disease Type 2k 12
Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type 2k 54
Charcot-Marie-Tooth Disease, Axonal, with Vocal Cord Paresis 50
Autosomal Dominant Charcot-Marie-Tooth Disease Type 2k 56
Charcot-Marie-Tooth Neuropathy Axonal Type 2k 12
Charcot-Marie-Tooth Disease Neuronal Type 2k 71
Charcot-Marie-Tooth Neuropathy Type 2k 71
Charcot-Marie-Tooth Disease 2k 71

Characteristics:

Orphanet epidemiological data:

56
autosomal recessive charcot-marie-tooth disease with hoarseness
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;
autosomal dominant charcot-marie-tooth disease type 2k
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Adolescent,Adult,Childhood;

OMIM:

54
Inheritance:
autosomal dominant
autosomal recessive

Miscellaneous:
allelic disorder to cmt4a
onset before age 3 years
onset in feet and legs (peroneal distribution)
upper limb involvement in first decade
severe progression
patients with autosomal dominant inheritance and a single gdap1 mutation have a less severe course with later onset
genetic heterogeneity (see cmt2a )


HPO:

32
charcot-marie-tooth disease, axonal, type 2k:
Onset and clinical course infantile onset
Inheritance heterogeneous autosomal recessive inheritance autosomal dominant inheritance


Classifications:

Orphanet: 56  
Rare neurological diseases


External Ids:

OMIM 54 607831
Disease Ontology 12 DOID:0110167
ICD10 33 G60.0
UMLS via Orphanet 70 C1842983 C1842984
ICD10 via Orphanet 34 G60.0
MeSH 42 D002607

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

NIH Rare Diseases : 50 the following summary is from orphanet, a european reference portal for information on rare diseases and orphan drugs.orpha number: 101097disease definitionautosomal recessive charcot-marie-tooth disease with hoarseness (arcmt2k or cmt4c4) is a severe early-onset form of axonal cmt peripheral sensorimotor polyneuropathy.epidemiologyarcmt2k was originally described in three spanish families and has since been described in five additional spanish kindreds, as well as in families from morocco, france and poland.clinical descriptiononset occurs in the neonatal period or early infancy with a clinical picture similar to that seen in cmt4a (another autosomal recessive form of cmt4 but with a demyelinating phenotype; see this term) including hypotonia, scoliosis, a hoarse voice, vocal cord paralysis and respiratory insufficiency. however, nerve conduction velocities and pathological findings from sural nerve biopsies in arcmt2k patients are indicative of a predominantly axonal neuropathy with some demyelinating features.etiologyarcmt2k is caused by mutations in the gdap1 gene (8q13.3), encoding a protein required for mitochondrial fission. mutations in the same gene are associated with cmt4a and with a milder, later-onset autosomal dominant axonal form of cmt, cmt2k (see this term).prognosisthe prognosis for arcmt2k may be severe, with two of the reported patients dying during in the fifth decade of life.visit the orphanet disease page for more resources. last updated: 1/19/2009

MalaCards based summary : Charcot-Marie-Tooth Disease, Axonal, Type 2k, also known as autosomal recessive charcot-marie-tooth disease with hoarseness, is related to charcot-marie-tooth disease, axonal, with vocal cord paresis and charcot-marie-tooth disease type 2g, and has symptoms including distal sensory impairment, kyphoscoliosis and talipes equinovarus. An important gene associated with Charcot-Marie-Tooth Disease, Axonal, Type 2k is GDAP1 (Ganglioside Induced Differentiation Associated Protein 1), and among its related pathways/superpathways are Cytoskeletal Signaling and Factors involved in megakaryocyte development and platelet production. Related phenotype is muscle.

UniProtKB/Swiss-Prot : 71 Charcot-Marie-Tooth disease 2K: An 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. Nerve conduction velocities are normal or slightly reduced. Charcot-Marie-Tooth disease type 2K onset is in early childhood (younger than 3 years). This phenotype is characterized by foot deformities, kyphoscoliosis, distal limb muscle weakness and atrophy, areflexia, and diminished sensation in the lower limbs. Weakness in the upper limbs is observed in the first decade, with clawing of the fingers. Inheritance can be autosomal dominant or recessive.

Disease Ontology : 12 A Charcot-Marie-Tooth disease type 2 that has material basis in homozygous or compound heterozygous mutation in the GDAP1 gene on chromosome 8q.

Description from OMIM: 607831

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

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

Charcot-Marie-Tooth Disease, Axonal, Type 2a2a Charcot-Marie-Tooth Disease, Axonal, Type 2a2b
Charcot-Marie-Tooth Disease, Axonal, Type 2t Charcot-Marie-Tooth Disease, Axonal, Type 2w
Charcot-Marie-Tooth Disease, Axonal, Type 2f Charcot-Marie-Tooth Disease, Axonal, Type 2h
Charcot-Marie-Tooth Disease, Axonal, Type 2k Charcot-Marie-Tooth Disease, Axonal, Type 2q
Charcot-Marie-Tooth Disease, Axonal, Type 2s Charcot-Marie-Tooth Disease, Axonal, Type 2u
Charcot-Marie-Tooth Disease, Axonal, Type 2l Charcot-Marie-Tooth Disease, Axonal, Type 20
Charcot-Marie-Tooth Disease, Axonal, Type 2x Charcot-Marie-Tooth Disease, Axonal, Type 2n
Charcot-Marie-Tooth Disease, Axonal, Type 2v Charcot-Marie-Tooth Disease, Axonal, Type 2z
Charcot-Marie-Tooth Disease, Axonal, Type 2cc

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

(show all 39)
id Related Disease Score Top Affiliating Genes
1 charcot-marie-tooth disease, axonal, with vocal cord paresis 35.1 GDAP1 JPH1 TUBB3
2 charcot-marie-tooth disease type 2g 32.9 KIF1B MFN2
3 charcot-marie-tooth disease type 2k 11.4
4 charcot-marie-tooth neuropathy type 2h/2k 10.8
5 ataxia with isolated vitamin e deficiency 10.6 DNAJB2 GDAP1
6 charcot-marie-tooth disease, type 2b1 10.6 DNAJB2 GDAP1 JPH1
7 glaucoma 1, open angle, 1o 10.6 DNAJB2 GDAP1 JPH1
8 ovarian clear cell carcinoma 10.5 TUBB TUBB2A
9 cataract 37 10.4 DNAJB2 MFN2
10 secondary syphilis 10.4 TUBB2A TUBB3
11 epileptic encephalopathy, early infantile, 29 10.4 KIF1B TRPV4
12 charcot-marie-tooth neuropathy x type 1 10.4 KIF1B MFN2
13 charcot-marie-tooth disease, type 2a1 10.4 KIF1B MFN2
14 hypertrophic osteoarthropathy, primary, autosomal recessive 2 10.3 KIF1B RAB7A
15 charcot-marie-tooth disease, type 1e 10.2 GDAP1 KIF1B MFN2
16 neuropathy, inflammatory demyelinating 10.2 GDAP1 KIF1B MFN2
17 orofacial cleft 12 10.1 GDAP1 MFN2 TRPV4
18 pituitary adenoma, growth hormone-secreting 10.1 DNAJB2 MFN2 TRPV4
19 infantile epileptic encephalopathy 10.1 KIF1B MFN2
20 skeletal muscle regeneration 10.1 HSPB3 HSPB8
21 epileptic encephalopathy, early infantile, 51 10.1 HSPB3 KIF1B
22 interstitial emphysema 10.0 NAA50 RAB7A
23 familial candidiasis 9.9 HSPB3 HSPB8 TUBB
24 transposition of the great arteries, dextro-looped 1 9.9 HSPB3 HSPB8 KIF1B
25 pseudosarcomatous fibromatosis 9.9 GDAP1 KIF5A MFN2 TRPV4
26 splenic marginal zone lymphoma 9.9 DNAJB2 DYNC1H1 TRPV4
27 dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema 9.8 KIF1A MFN2
28 pancreatic acinar cell adenocarcinoma 9.8 GDAP1 MFN2 NAA50 TUBB3
29 mitochondrial complex i deficiency 9.8
30 charcot-marie-tooth disease 9.8
31 tooth disease 9.8
32 pleomorphic carcinoma 9.7 FIS1 MFN2 TUBB3
33 scapuloperoneal spinal muscular atrophy 9.5 GDAP1 KIF1B MFN2 RAB7A TRPV4
34 thrombophilia due to antithrombin iii deficiency 9.0 DNAJB2 DYNC1H1 GDAP1 HSPB8 KIF1B MFN2
35 neuropathy, congenital hypomyelinating 8.7 DYNC1H1 GDAP1 HSPB8 JPH1 KIF1B MFN2
36 amnestic disorder 8.6 DNM2 GDAP1 HSPB8 KIF1B MFN2 RAB7A
37 charcot-marie-tooth disease, type 1f 8.5 DNAJB2 GDAP1 HSPB8 JPH1 KIF1B MFN2
38 childhood-onset cerebral x-linked adrenoleukodystrophy 7.9 DNAJB2 DNM2 DYNC1H1 GDAP1 HSPB8 JPH1
39 charcot-marie-tooth disease, recessive intermediate, a 4.6 DNAJB2 DNM2 DYNC1H1 FIS1 GDAP1 HSPB3

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



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

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

Symptoms via clinical synopsis from OMIM:

54

Neurologic- Peripheral Nervous System:
distal limb muscle weakness due to peripheral neuropathy
distal limb muscle atrophy due to peripheral neuropathy
distal sensory impairment
axonal regeneration on nerve biopsy
areflexia
more
Skeletal- Feet:
talipes equinovarus

Skeletal- Spine:
kyphoscoliosis

Skeletal- Hands:
claw hand deformities


Clinical features from OMIM:

607831

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

32 (show all 11)
id Description HPO Frequency HPO Source Accession
1 distal sensory impairment 32 HP:0002936
2 kyphoscoliosis 32 HP:0002751
3 talipes equinovarus 32 HP:0001762
4 areflexia 32 HP:0001284
5 distal muscle weakness 32 HP:0002460
6 proximal muscle weakness 32 HP:0003701
7 distal amyotrophy 32 HP:0003693
8 axonal regeneration 32 HP:0003450
9 split hand 32 HP:0001171
10 decreased motor nerve conduction velocity 32 HP:0003431
11 decreased number of peripheral myelinated nerve fibers 32 HP:0003380

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

44
id Description MGI Source Accession Score Top Affiliating Genes
1 muscle MP:0005369 9.17 DNM2 DYNC1H1 HSPB8 JPH1 KIF1B MFN2

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

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

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

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

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

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

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

71
id Symbol AA change Variation ID SNP ID
1 GDAP1 p.His256Arg VAR_067086
2 GDAP1 p.Arg282His VAR_067087 rs375431837
3 GDAP1 p.Arg120Gly VAR_078265
4 GDAP1 p.Arg120Trp VAR_078266 rs104894078
5 GDAP1 p.His123Arg VAR_078267 rs397515442
6 GDAP1 p.Ala156Gly VAR_078269 rs397515441
7 GDAP1 p.Arg310Trp VAR_078273 rs538389475

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

6 (show all 11)
id Gene Variation Type Significance SNP ID Assembly Location
1 GDAP1 NM_018972.2(GDAP1): c.581C> G (p.Ser194Ter) single nucleotide variant Pathogenic rs104894075 GRCh37 Chromosome 8, 75275175: 75275175
2 GDAP1 NM_018972.2(GDAP1): c.358C> T (p.Arg120Trp) single nucleotide variant Pathogenic rs104894078 GRCh37 Chromosome 8, 75272419: 75272419
3 GDAP1 NM_018972.2(GDAP1): c.469A> C (p.Thr157Pro) single nucleotide variant Pathogenic rs104894079 GRCh37 Chromosome 8, 75272530: 75272530
4 GDAP1 NM_018972.2(GDAP1): c.715C> T (p.Leu239Phe) single nucleotide variant Pathogenic rs104894080 GRCh37 Chromosome 8, 75276240: 75276240
5 GDAP1 NM_018972.2(GDAP1): c.652C> G (p.Gln218Glu) single nucleotide variant Pathogenic rs121908113 GRCh37 Chromosome 8, 75275246: 75275246
6 GDAP1 NM_018972.2(GDAP1): c.692C> T (p.Pro231Leu) single nucleotide variant Pathogenic/Likely pathogenic rs121908114 GRCh37 Chromosome 8, 75275286: 75275286
7 GDAP1 NM_018972.2(GDAP1): c.719G> A (p.Cys240Tyr) single nucleotide variant Pathogenic rs121908115 GRCh37 Chromosome 8, 75276244: 75276244
8 GDAP1 NM_018972.2(GDAP1): c.678A> T (p.Arg226Ser) single nucleotide variant Pathogenic rs267606842 GRCh37 Chromosome 8, 75275272: 75275272
9 GDAP1 NM_018972.2(GDAP1): c.467C> G (p.Ala156Gly) single nucleotide variant Pathogenic rs397515441 GRCh37 Chromosome 8, 75272528: 75272528
10 GDAP1 NM_018972.2(GDAP1): c.368A> G (p.His123Arg) single nucleotide variant Pathogenic rs397515442 GRCh37 Chromosome 8, 75272429: 75272429
11 GDAP1 NM_018972.2(GDAP1): c.821C> T (p.Pro274Leu) single nucleotide variant Pathogenic rs397515443 GRCh37 Chromosome 8, 75276346: 75276346

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

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

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

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

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

id Name GO ID Score Top Affiliating Genes
1 cytoskeleton GO:0005856 9.56 DNM2 DYNC1H1 KIF1A KIF1B KIF5A TUBB
2 microtubule cytoskeleton GO:0015630 9.46 MFN2 TUBB TUBB2A TUBB3
3 kinesin complex GO:0005871 9.43 KIF1A KIF1B KIF5A
4 integral component of mitochondrial outer membrane GO:0031307 9.37 FIS1 GDAP1
5 microtubule GO:0005874 9.23 DNM2 DYNC1H1 KIF1A KIF1B KIF5A TUBB
6 cytoplasm GO:0005737 10.17 DNAJB2 DNM2 DYNC1H1 GDAP1 HSPB3 HSPB8

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

id Name GO ID Score Top Affiliating Genes
1 G2/M transition of mitotic cell cycle GO:0000086 9.63 DNM2 DYNC1H1 TUBB
2 antigen processing and presentation of exogenous peptide antigen via MHC class II GO:0019886 9.62 DNM2 DYNC1H1 KIF5A RAB7A
3 response to unfolded protein GO:0006986 9.61 DNAJB2 HSPB3 MFN2
4 microtubule-based process GO:0007017 9.58 TUBB TUBB2A TUBB3
5 protein targeting to mitochondrion GO:0006626 9.54 FIS1 GDAP1 MFN2
6 anterograde axonal transport GO:0008089 9.48 KIF1A KIF1B
7 microtubule-based movement GO:0007018 9.46 DYNC1H1 KIF1A KIF1B KIF5A
8 mitochondrial fission GO:0000266 9.43 DNM2 FIS1 GDAP1
9 cytoskeleton-dependent intracellular transport GO:0030705 9.13 KIF1B KIF5A TUBB
10 mitochondrial fusion GO:0008053 8.8 FIS1 GDAP1 MFN2

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

id Name GO ID Score Top Affiliating Genes
1 nucleotide binding GO:0000166 9.67 DNM2 DYNC1H1 TRPV4 TUBB
2 microtubule binding GO:0008017 9.65 DNM2 KIF1A KIF1B KIF5A TRPV4
3 motor activity GO:0003774 9.62 DYNC1H1 KIF1A KIF1B KIF5A
4 structural constituent of cytoskeleton GO:0005200 9.58 TUBB TUBB2A TUBB3
5 microtubule motor activity GO:0003777 9.46 DYNC1H1 KIF1A KIF1B KIF5A
6 GTP binding GO:0005525 9.43 DNM2 MFN2 RAB7A TUBB TUBB2A TUBB3
7 GTPase activity GO:0003924 9.1 DNM2 MFN2 RAB7A TUBB TUBB2A TUBB3

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

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
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33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
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42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
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48 NDF-RT
51 NINDS
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55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
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70 UMLS via Orphanet
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