MCID: CHR517
MIFTS: 39

Charcot-Marie-Tooth Disease, Type 4a

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

Aliases & Classifications for Charcot-Marie-Tooth Disease, Type 4a

MalaCards integrated aliases for Charcot-Marie-Tooth Disease, Type 4a:

Name: Charcot-Marie-Tooth Disease, Type 4a 53 28 13 69
Cmt4a 53 12 49 55 71
Charcot-Marie-Tooth Disease Type 4a 12 49 55 14
Charcot-Marie-Tooth Disease, Demyelinating, Autosomal Recessive, Type 4a 53
Charcot-Marie-Tooth Disease Demyelinating Autosomal Recessive, Type 4a 71
Autosomal Recessive Demyelinating Charcot-Marie-Tooth Disease Type 4a 12
Charcot-Marie-Tooth Disease, Demyelinating, Autosomal Recessive 49
Charcot-Marie-Tooth Disease Neuropathy Type 4a 71
Charcot-Marie-Tooth Neuropathy, Type 4a 53
Charcot-Marie-Tooth Neuropathy Type 4a 12
Charcot Marie Tooth Disease Type 4a 49
Charcot-Marie-Tooth Disease 4a 71

Characteristics:

Orphanet epidemiological data:

55
charcot-marie-tooth disease type 4a
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
genetic heterogeneity
usually begins in feet and legs (peroneal distribution)
upper limb involvement usually occurs later
onset before age 2 years
rapid progression to disability


HPO:

31
charcot-marie-tooth disease, type 4a:
Onset and clinical course rapidly progressive infantile onset
Inheritance heterogeneous autosomal recessive inheritance


Classifications:

Orphanet: 55  
Rare neurological diseases


External Ids:

OMIM 53 214400
Disease Ontology 12 DOID:0110185
ICD10 32 G60.0
Orphanet 55 ORPHA99948
MESH via Orphanet 42 C535419
UMLS via Orphanet 70 C1859198
ICD10 via Orphanet 33 G60.0
MedGen 39 C1859198
MeSH 41 D002607
UMLS 69 C1859198

Summaries for Charcot-Marie-Tooth Disease, Type 4a

UniProtKB/Swiss-Prot : 71 Charcot-Marie-Tooth disease 4A: A recessive demyelinating 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). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. By convention autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease are designated CMT4. CMT4A is a severe form characterized by early age of onset and rapid progression leading to inability to walk in late childhood or adolescence.

MalaCards based summary : Charcot-Marie-Tooth Disease, Type 4a, also known as cmt4a, is related to charcot-marie-tooth disease, axonal, type 2k and charcot-marie-tooth disease, type 4j, and has symptoms including decreased motor nerve conduction velocity, areflexia and split hand. An important gene associated with Charcot-Marie-Tooth Disease, Type 4a is GDAP1 (Ganglioside Induced Differentiation Associated Protein 1). The drugs 4-des-dimethylaminotetracycline and HIV Protease Inhibitors have been mentioned in the context of this disorder. Related phenotypes are behavior/neurological and nervous system

OMIM : 53 By convention, the designation CMT4 is applied to autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease, which is a peripheral neuropathy characterized by distal motor and sensory impairment resulting in gait difficulties and associated with foot deformities. Motor nerve conduction velocities are decreased, and sural nerve biopsies show loss of myelinated fibers. The age at onset and severity is variable (summary by Patzko and Shy, 2012). (214400)

Disease Ontology : 12 A Charcot-Marie-Tooth disease type 4 that has material basis in mutation in the gene encoding ganglioside-induced differentiation-associated protein-1 (GDAP1) on chromosome 8q21.

Related Diseases for Charcot-Marie-Tooth Disease, Type 4a

Diseases in the Charcot-Marie-Tooth Disease family:

Charcot-Marie-Tooth Disease, Type 4a Charcot-Marie-Tooth Disease, Type 4b1
Charcot-Marie-Tooth Disease, Type 4d Charcot-Marie-Tooth Disease, Type 4c
Charcot-Marie-Tooth Disease, Type 4b2 Charcot-Marie-Tooth Disease, Dominant Intermediate B
Charcot-Marie-Tooth Disease, Dominant Intermediate a Charcot-Marie-Tooth Disease, Dominant Intermediate C
Charcot-Marie-Tooth Disease, Recessive Intermediate a Charcot-Marie-Tooth Disease, Type 4h
Charcot-Marie-Tooth Disease, Type 4j Charcot-Marie-Tooth Disease, Recessive Intermediate B
Charcot-Marie-Tooth Disease, Type 4b3 Charcot-Marie-Tooth Disease, Recessive Intermediate C
Charcot-Marie-Tooth Disease, Type 4k Charcot-Marie-Tooth Disease Intermediate Type
Charcot-Marie-Tooth Disease Type 5 Charcot-Marie-Tooth Disease Type 7
Charcot-Marie-Tooth Disease Type 2a2 Autosomal Dominant Intermediate Charcot-Marie-Tooth
Autosomal Dominant Intermediate Charcot-Marie-Tooth Disease Type B Autosomal Recessive Intermediate Charcot-Marie-Tooth Disease
Charcot-Marie-Tooth Disease Type 2a Charcot-Marie-Tooth Disease Type 2c
Charcot-Marie-Tooth Disease Type 2f Charcot-Marie-Tooth Disease Type 2g
Charcot-Marie-Tooth Disease Type 2k Charcot-Marie-Tooth Disease Type 2l
Charcot-Marie-Tooth Disease Type 2n Charcot-Marie-Tooth Disease Type 2o
Charcot-Marie-Tooth Disease Type 2q Autosomal Dominant Charcot-Marie-Tooth Disease Type 2 Due to Kif5a Mutation
Autosomal Dominant Charcot-Marie-Tooth Disease Type 2 Due to Tfg Mutation Autosomal Dominant Charcot-Marie-Tooth Disease Type 2 Due to Dgat2 Mutation
Autosomal Dominant Charcot-Marie-Tooth Disease Type 2g

Diseases related to Charcot-Marie-Tooth Disease, Type 4a via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 34)
# Related Disease Score Top Affiliating Genes
1 charcot-marie-tooth disease, axonal, type 2k 31.4 GDAP1 JPH1 TUBB3
2 charcot-marie-tooth disease, type 4j 30.9 GDAP1 MTMR2 SBF2
3 charcot-marie-tooth disease, type 4b2 30.3 GDAP1 MTMR2 PRX SBF2
4 neuropathy, congenital hypomyelinating or amyelinating, autosomal recessive 30.1 GDAP1 JPH1 MTMR2 PRX SBF2
5 neuropathy 30.0 GDAP1 PRX TDP1
6 charcot-marie-tooth disease, demyelinating, type 4f 29.8 GDAP1 MTMR2 PRX SBF2 TDP1
7 tooth disease 29.7 GDAP1 MTMR2 PRX SBF2
8 charcot-marie-tooth disease 28.4 GDAP1 JPH1 MTMR2 PMP2 PRX SBF2
9 charcot-marie-tooth disease, type 4c 11.7
10 charcot-marie-tooth disease, type 4h 11.7
11 charcot-marie-tooth disease, axonal, with vocal cord paresis, autosomal recessive 11.4
12 charcot-marie-tooth disease type 2g 11.4
13 charcot-marie-tooth disease, axonal, type 2a1 10.8
14 charcot-marie-tooth disease, type 4d 10.8
15 neuropathy, hereditary motor and sensory, russe type 10.8
16 charcot-marie-tooth disease, axonal, autosomal dominant, type 2a2a 10.8
17 charcot-marie-tooth disease, type 4k 10.8
18 neuronitis 10.3
19 charcot-marie-tooth disease type 2k 10.2 GDAP1 JPH1
20 charcot-marie-tooth disease, demyelinating, type 1a 10.1 GDAP1 MTMR2
21 myoclonic epilepsy associated with ragged-red fibers 10.1 GDAP1 JPH1
22 charcot-marie-tooth disease and deafness 10.0 GDAP1 MTMR2
23 hereditary neuropathies 10.0 MTMR2 PRX
24 early-onset glaucoma 9.9 MTMR2 SBF2
25 peripheral nervous system disease 9.9 GDAP1 MTMR2 TUBB3
26 centronuclear myopathy 9.9 MTMR2 SBF2
27 axonal neuropathy 9.9 GDAP1 TDP1
28 hypertrophic neuropathy of dejerine-sottas 9.8 GDAP1 MTMR2 PRX
29 sensory peripheral neuropathy 9.8 GDAP1 MTMR2 PRX
30 polyneuropathy 9.8 GDAP1 TUBB3
31 charcot-marie-tooth disease, type 4b3 9.8 GDAP1 MTMR2 SBF2
32 congenital hypomyelination neuropathy 9.6 MTMR2 PRX SBF2
33 charcot-marie-tooth disease, axonal, type 2e 9.5 GDAP1 JPH1 MTMR2 SBF2
34 charcot-marie-tooth disease, type 4b1 9.4 GDAP1 MTMR2 PRX SBF2

Graphical network of the top 20 diseases related to Charcot-Marie-Tooth Disease, Type 4a:



Diseases related to Charcot-Marie-Tooth Disease, Type 4a

Symptoms & Phenotypes for Charcot-Marie-Tooth Disease, Type 4a

Symptoms via clinical synopsis from OMIM:

53
Neurologic Peripheral Nervous System:
areflexia
hyporeflexia
distal sensory impairment
hypertrophic nerve changes
delayed motor development
more
Skeletal Hands:
claw hand deformities (in severe cases)

Skeletal Spine:
kyphoscoliosis may occur

Skeletal Feet:
foot deformities may occur


Clinical features from OMIM:

214400

Human phenotypes related to Charcot-Marie-Tooth Disease, Type 4a:

31 (show all 18)
# Description HPO Frequency HPO Source Accession
1 decreased motor nerve conduction velocity 31 HP:0003431
2 areflexia 31 HP:0001284
3 split hand 31 HP:0001171
4 hyporeflexia 31 HP:0001265
5 motor delay 31 HP:0001270
6 kyphoscoliosis 31 frequent (33%) HP:0002751
7 hammertoe 31 HP:0001765
8 distal muscle weakness 31 HP:0002460
9 cns hypomyelination 31 HP:0003429
10 distal sensory impairment 31 HP:0002936
11 distal amyotrophy 31 HP:0003693
12 decreased number of peripheral myelinated nerve fibers 31 HP:0003380
13 hypertrophic nerve changes 31 HP:0003382
14 inability to walk by childhood/adolescence 31 HP:0006915
15 ulnar claw 31 HP:0001178
16 peripheral axonal degeneration 31 HP:0000764
17 basal lamina 'onion bulb' formation 31 HP:0003400
18 peripheral hypomyelination 31 HP:0007182

MGI Mouse Phenotypes related to Charcot-Marie-Tooth Disease, Type 4a:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.5 GDAP1 JPH1 MTMR2 PMP2 PRX SBF2
2 nervous system MP:0003631 9.17 GDAP1 MTMR2 PMP2 PRX SBF2 TDP1

Drugs & Therapeutics for Charcot-Marie-Tooth Disease, Type 4a

Drugs for Charcot-Marie-Tooth Disease, Type 4a (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 4-des-dimethylaminotetracycline
2 HIV Protease Inhibitors
3 Matrix Metalloproteinase Inhibitors
4
protease inhibitors

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Natural History Evaluation of Charcot Marie Tooth Disease (CMT) Types CMT1B, CMT2A, CMT4A, CMT4C, and Others Recruiting NCT01193075

Search NIH Clinical Center for Charcot-Marie-Tooth Disease, Type 4a

Genetic Tests for Charcot-Marie-Tooth Disease, Type 4a

Genetic tests related to Charcot-Marie-Tooth Disease, Type 4a:

# Genetic test Affiliating Genes
1 Charcot-Marie-Tooth Disease, Type 4a 28 GDAP1

Anatomical Context for Charcot-Marie-Tooth Disease, Type 4a

Publications for Charcot-Marie-Tooth Disease, Type 4a

Articles related to Charcot-Marie-Tooth Disease, Type 4a:

# Title Authors Year
1
GDAP1, the protein causing Charcot-Marie-Tooth disease type 4A, is expressed in neurons and is associated with mitochondria. ( 15772096 )
2005
2
Genetics of Charcot-Marie-Tooth disease type 4A: mutations, inheritance, phenotypic variability, and founder effect. ( 15805163 )
2005

Variations for Charcot-Marie-Tooth Disease, Type 4a

UniProtKB/Swiss-Prot genetic disease variations for Charcot-Marie-Tooth Disease, Type 4a:

71
# Symbol AA change Variation ID SNP ID
1 GDAP1 p.Arg120Gln VAR_017184
2 GDAP1 p.Arg161His VAR_017185 rs104894076

ClinVar genetic disease variations for Charcot-Marie-Tooth Disease, Type 4a:

6 (show all 15)
# Gene Variation Type Significance SNP ID Assembly Location
1 GDAP1 NM_018972.2(GDAP1): c.347T> G (p.Met116Arg) single nucleotide variant Pathogenic rs281865060 GRCh38 Chromosome 8, 74360173: 74360173
2 GDAP1 NM_018972.2(GDAP1): c.92G> A (p.Trp31Ter) single nucleotide variant Pathogenic rs121908112 GRCh37 Chromosome 8, 75262788: 75262788
3 GDAP1 NM_018972.2(GDAP1): c.581C> G (p.Ser194Ter) single nucleotide variant Pathogenic rs104894075 GRCh37 Chromosome 8, 75275175: 75275175
4 GDAP1 NM_018972.2(GDAP1): c.482G> A (p.Arg161His) single nucleotide variant Pathogenic rs104894076 GRCh37 Chromosome 8, 75272543: 75272543
5 GDAP1 NM_018972.2(GDAP1): c.487C> T (p.Gln163Ter) single nucleotide variant Pathogenic rs104894077 GRCh37 Chromosome 8, 75274121: 75274121
6 GDAP1 NM_018972.2(GDAP1): c.358C> T (p.Arg120Trp) single nucleotide variant Pathogenic rs104894078 GRCh37 Chromosome 8, 75272419: 75272419
7 GDAP1 NM_018972.2(GDAP1): c.715C> T (p.Leu239Phe) single nucleotide variant Pathogenic rs104894080 GRCh37 Chromosome 8, 75276240: 75276240
8 GDAP1 NM_018972.2(GDAP1): c.373C> T (p.Arg125Ter) single nucleotide variant Pathogenic rs745663149 GRCh38 Chromosome 8, 74360199: 74360199
9 GDAP1 NM_018972.2(GDAP1): c.579+1G> A single nucleotide variant Pathogenic rs864622501 GRCh37 Chromosome 8, 75274214: 75274214
10 GDAP1 NM_018972.2(GDAP1): c.579delA (p.Lys193Asnfs) deletion Pathogenic rs1060500979 GRCh38 Chromosome 8, 74361978: 74361978
11 GDAP1 NM_018972.2(GDAP1): c.786delG (p.Phe263Leufs) deletion Pathogenic/Likely pathogenic rs1060500978 GRCh38 Chromosome 8, 74364076: 74364076
12 GDAP1 NM_018972.2(GDAP1): c.1019dupT (p.Arg341Glnfs) duplication Likely pathogenic rs756461496 GRCh38 Chromosome 8, 74364309: 74364309
13 GDAP1 NM_018972.2(GDAP1): c.311-1790_408del deletion Likely pathogenic GRCh38 Chromosome 8, 74358347: 74360234
14 GDAP1 NM_018972.2(GDAP1): c.703C> T (p.Gln235Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 8, 74363993: 74363993
15 GDAP1 NM_018972.2(GDAP1): c.503_504delAG (p.Glu168Valfs) deletion Pathogenic GRCh38 Chromosome 8, 74361902: 74361903

Expression for Charcot-Marie-Tooth Disease, Type 4a

Search GEO for disease gene expression data for Charcot-Marie-Tooth Disease, Type 4a.

Pathways for Charcot-Marie-Tooth Disease, Type 4a

GO Terms for Charcot-Marie-Tooth Disease, Type 4a

Cellular components related to Charcot-Marie-Tooth Disease, Type 4a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 9.5 GDAP1 MTMR2 PMP2 PRX SBF2 TDP1
2 vacuolar membrane GO:0005774 8.62 MTMR2 SBF2

Biological processes related to Charcot-Marie-Tooth Disease, Type 4a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein tetramerization GO:0051262 8.62 MTMR2 SBF2

Sources for Charcot-Marie-Tooth Disease, Type 4a

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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