MCID: CHR516
MIFTS: 37

Charcot-Marie-Tooth Disease, Type 4c

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

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

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

Name: Charcot-Marie-Tooth Disease, Type 4c 57 29 13 6 40 73
Charcot-Marie-Tooth Disease Type 4c 12 24 53 59 15
Cmt4c 57 12 24 59 75
Charcot-Marie-Tooth Neuropathy Type 4c 12 24 75
Charcot-Marie-Tooth Disease, Demyelinating, Autosomal Recessive, Type 4c 57 53
Charcot-Marie-Tooth Neuropathy, Type 4c 57 53
Autosomal Recessive Demyelinating Charcot-Marie-Tooth Disease Type 4c 12
Charcot-Marie-Tooth Disease Demyelinating Autosomal Recessive 4c 75
Charcot Marie Tooth Disease Type 4c 53
Charcot-Marie-Tooth Disease 4c 75
Cmt 4c 53

Characteristics:

Orphanet epidemiological data:

59
charcot-marie-tooth disease type 4c
Inheritance: Autosomal recessive; Age of onset: Childhood;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
usually begins in feet and legs (peroneal distribution)
highly variable phenotype, even within families
onset usually in first or second decades
later onset has been reported (third or fourth decades)
patients may become wheelchair-bound
genetic heterogeneity (see cmt4a )
prevalent among european, particularly spanish, gypsies (r1109x, )


HPO:

32
charcot-marie-tooth disease, type 4c:
Onset and clinical course phenotypic variability
Inheritance heterogeneous autosomal recessive inheritance


Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

OMIM 57 601596
Disease Ontology 12 DOID:0110183
ICD10 33 G60.0
Orphanet 59 ORPHA99949
UMLS via Orphanet 74 C1866636
ICD10 via Orphanet 34 G60.0
MESH via Orphanet 45 C535423
MedGen 42 C1866636
MeSH 44 D002607
UMLS 73 C1866636

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

UniProtKB/Swiss-Prot : 75 Charcot-Marie-Tooth disease 4C: 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. CMT4C is characterized by onset in childhood, early-onset scoliosis and a distinct Schwann cell pathology.

MalaCards based summary : Charcot-Marie-Tooth Disease, Type 4c, also known as charcot-marie-tooth disease type 4c, is related to neuropathy, congenital hypomyelinating or amyelinating, autosomal recessive and charcot-marie-tooth disease, and has symptoms including facial paresis An important gene associated with Charcot-Marie-Tooth Disease, Type 4c is SH3TC2 (SH3 Domain And Tetratricopeptide Repeats 2), and among its related pathways/superpathways are Vasopressin-regulated water reabsorption and Melanocyte Development and Pigmentation. The drugs 4-des-dimethylaminotetracycline and HIV Protease Inhibitors have been mentioned in the context of this disorder. Affiliated tissues include tongue, and related phenotypes are hearing impairment and nystagmus

Disease Ontology : 12 A Charcot-Marie-Tooth disease type 4 that has material basis in homozygous or compound heterozygous mutation in the SH3TC2 gene.

Description from OMIM: 601596
GeneReviews: NBK1340

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

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 Dnajb2-Related Charcot-Marie-Tooth Disease Type 2
Pmp2-Related Charcot-Marie-Tooth Disease Type 1 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 4c via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 neuropathy, congenital hypomyelinating or amyelinating, autosomal recessive 11.1
2 charcot-marie-tooth disease 10.8
3 tooth disease 10.8
4 neuropathy 10.3
5 peripheral nervous system disease 9.9

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



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

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

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
nystagmus
abnormal pupillary light reflexes

Neurologic Peripheral Nervous System:
difficulty walking
decreased motor nerve conduction velocity (ncv) (less than 38 m/s)
loss of large myelinated fibers
basal lamina 'onion bulb' formations on nerve biopsy
cranial nerve involvement
more
Neurologic Central Nervous System:
delayed motor development

Head And Neck Face:
facial weakness
cranial nerve involvement

Skeletal Feet:
pes cavus
foot deformities

Head And Neck Mouth:
tongue fasciculations
tongue atrophy
tongue weakness

Head And Neck Ears:
deafness
prolonged brainstem auditory evoked potentials (baep)

Skeletal Spine:
scoliosis, early-onset, severe


Clinical features from OMIM:

601596

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

32 (show all 21)
# Description HPO Frequency HPO Source Accession
1 hearing impairment 32 HP:0000365
2 nystagmus 32 HP:0000639
3 peripheral axonal degeneration 32 HP:0000764
4 motor delay 32 HP:0001270
5 abnormality of the cranial nerves 32 HP:0001291
6 tongue fasciculations 32 HP:0001308
7 pes cavus 32 HP:0001761
8 difficulty walking 32 HP:0002355
9 distal muscle weakness 32 HP:0002460
10 scoliosis 32 HP:0002650
11 distal sensory impairment 32 HP:0002936
12 decreased number of large peripheral myelinated nerve fibers 32 HP:0003387
13 basal lamina 'onion bulb' formation 32 HP:0003400
14 decreased motor nerve conduction velocity 32 HP:0003431
15 upper limb muscle weakness 32 HP:0003484
16 distal amyotrophy 32 HP:0003693
17 prolonged brainstem auditory evoked potentials 32 HP:0004466
18 segmental peripheral demyelination 32 HP:0007107
19 abnormal pupillary light reflex 32 HP:0007695
20 facial palsy 32 HP:0010628
21 tongue atrophy 32 HP:0012473

UMLS symptoms related to Charcot-Marie-Tooth Disease, Type 4c:


facial paresis

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

Drugs for Charcot-Marie-Tooth Disease, Type 4c (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 4c

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

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

# Genetic test Affiliating Genes
1 Charcot-Marie-Tooth Disease, Type 4c 29 SH3TC2

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

MalaCards organs/tissues related to Charcot-Marie-Tooth Disease, Type 4c:

41
Tongue

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

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

# Title Authors Year
1
Exclusive expression of the Rab11 effector SH3TC2 in Schwann cells links integrin-I+6 and myelin maintenance to Charcot-Marie-Tooth disease type 4C. ( 27068304 )
2016
2
[Mutation analysis for a family affected with Charcot-Marie-Tooth disease type 4C]. ( 26829735 )
2016
3
Novel mutations in SH3TC2 in a young Japanese girl with Charcot-Marie-Tooth disease type 4C. ( 27882734 )
2016
4
Haplotype-specific modulation of a SOX10/CREB response element at the Charcot-Marie-Tooth disease type 4C locus SH3TC2. ( 24833716 )
2014
5
Charcot-Marie-Tooth disease type 4C in Japan: report of a case. ( 23281072 )
2013
6
Mistargeting of SH3TC2 away from the recycling endosome causes Charcot-Marie-Tooth disease type 4C. ( 20028792 )
2010
7
Missense mutations in the SH3TC2 protein causing Charcot-Marie-Tooth disease type 4C affect its localization in the plasma membrane and endocytic pathway. ( 19744956 )
2009
8
The phenotype of Charcot-Marie-Tooth disease type 4C due to SH3TC2 mutations and possible predisposition to an inflammatory neuropathy. ( 19272779 )
2009
9
The kinesin superfamily protein Rab6KIFL is not involved in the pathophysiology of Charcot-Marie-Tooth disease type 4C. ( 12469216 )
2003

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

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

75
# Symbol AA change Variation ID SNP ID
1 SH3TC2 p.Arg529Gln VAR_018268 rs863224454
2 SH3TC2 p.Glu657Lys VAR_018269 rs80338925
3 SH3TC2 p.Arg658Cys VAR_018270 rs80338926

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

6
(show all 46)
# Gene Variation Type Significance SNP ID Assembly Location
1 SH3TC2 NM_024577.3(SH3TC2): c.1586G> A (p.Arg529His) single nucleotide variant Pathogenic rs80338923 GRCh37 Chromosome 5, 148407709: 148407709
2 SH3TC2 NM_024577.3(SH3TC2): c.1586G> A (p.Arg529His) single nucleotide variant Pathogenic rs80338923 GRCh38 Chromosome 5, 149028146: 149028146
3 SH3TC2 NM_024577.3(SH3TC2): c.1747_1748delAG (p.Arg583Alafs) deletion Pathogenic rs80338924 GRCh37 Chromosome 5, 148407547: 148407548
4 SH3TC2 NM_024577.3(SH3TC2): c.1747_1748delAG (p.Arg583Alafs) deletion Pathogenic rs80338924 GRCh38 Chromosome 5, 149027984: 149027985
5 SH3TC2 NM_024577.3(SH3TC2): c.530-2A> G single nucleotide variant Pathogenic rs80338920 GRCh37 Chromosome 5, 148421182: 148421182
6 SH3TC2 NM_024577.3(SH3TC2): c.530-2A> G single nucleotide variant Pathogenic rs80338920 GRCh38 Chromosome 5, 149041619: 149041619
7 SH3TC2 NM_024577.3(SH3TC2): c.2829T> G (p.Tyr943Ter) single nucleotide variant Pathogenic rs80338932 GRCh37 Chromosome 5, 148406466: 148406466
8 SH3TC2 NM_024577.3(SH3TC2): c.2829T> G (p.Tyr943Ter) single nucleotide variant Pathogenic rs80338932 GRCh38 Chromosome 5, 149026903: 149026903
9 SH3TC2 NM_024577.3(SH3TC2): c.2860C> T (p.Arg954Ter) single nucleotide variant Pathogenic rs80338933 GRCh37 Chromosome 5, 148406435: 148406435
10 SH3TC2 NM_024577.3(SH3TC2): c.2860C> T (p.Arg954Ter) single nucleotide variant Pathogenic rs80338933 GRCh38 Chromosome 5, 149026872: 149026872
11 SH3TC2 NM_024577.3(SH3TC2): c.3325C> T (p.Arg1109Ter) single nucleotide variant Pathogenic rs80338934 GRCh37 Chromosome 5, 148389835: 148389835
12 SH3TC2 NM_024577.3(SH3TC2): c.3325C> T (p.Arg1109Ter) single nucleotide variant Pathogenic rs80338934 GRCh38 Chromosome 5, 149010272: 149010272
13 SH3TC2 NM_024577.3(SH3TC2): c.1178-1G> A single nucleotide variant Pathogenic rs80338922 GRCh37 Chromosome 5, 148408118: 148408118
14 SH3TC2 NM_024577.3(SH3TC2): c.1178-1G> A single nucleotide variant Pathogenic rs80338922 GRCh38 Chromosome 5, 149028555: 149028555
15 SH3TC2 NM_024577.3(SH3TC2): c.1969G> A (p.Glu657Lys) single nucleotide variant Pathogenic rs80338925 GRCh37 Chromosome 5, 148407326: 148407326
16 SH3TC2 NM_024577.3(SH3TC2): c.1969G> A (p.Glu657Lys) single nucleotide variant Pathogenic rs80338925 GRCh38 Chromosome 5, 149027763: 149027763
17 SH3TC2 NM_024577.3(SH3TC2): c.1972C> T (p.Arg658Cys) single nucleotide variant Likely pathogenic rs80338926 GRCh37 Chromosome 5, 148407323: 148407323
18 SH3TC2 NM_024577.3(SH3TC2): c.1972C> T (p.Arg658Cys) single nucleotide variant Likely pathogenic rs80338926 GRCh38 Chromosome 5, 149027760: 149027760
19 SH3TC2 NM_024577.3(SH3TC2): c.1982T> C (p.Leu661Pro) single nucleotide variant Pathogenic rs80338927 GRCh37 Chromosome 5, 148407313: 148407313
20 SH3TC2 NM_024577.3(SH3TC2): c.1982T> C (p.Leu661Pro) single nucleotide variant Pathogenic rs80338927 GRCh38 Chromosome 5, 149027750: 149027750
21 SH3TC2 NM_024577.3(SH3TC2): c.217_227delGCTGCTCGGAGinsCCAGTAA (p.Ala73Profs) indel Pathogenic rs80338919 GRCh37 Chromosome 5, 148427477: 148427487
22 SH3TC2 NM_024577.3(SH3TC2): c.217_227delGCTGCTCGGAGinsCCAGTAA (p.Ala73Profs) indel Pathogenic rs80338919 GRCh38 Chromosome 5, 149047914: 149047924
23 SH3TC2 NM_024577.3(SH3TC2): c.2191delG (p.Glu731Lysfs) deletion Pathogenic rs80338928 GRCh37 Chromosome 5, 148407104: 148407104
24 SH3TC2 NM_024577.3(SH3TC2): c.2191delG (p.Glu731Lysfs) deletion Pathogenic rs80338928 GRCh38 Chromosome 5, 149027541: 149027541
25 SH3TC2 NM_024577.3(SH3TC2): c.2491_2492delAG (p.Leu832Hisfs) deletion Pathogenic rs80338929 GRCh37 Chromosome 5, 148406803: 148406804
26 SH3TC2 NM_024577.3(SH3TC2): c.2491_2492delAG (p.Leu832Hisfs) deletion Pathogenic rs80338929 GRCh38 Chromosome 5, 149027240: 149027241
27 SH3TC2 NM_024577.3(SH3TC2): c.2642A> T (p.Asn881Ile) single nucleotide variant Pathogenic rs80338930 GRCh37 Chromosome 5, 148406653: 148406653
28 SH3TC2 NM_024577.3(SH3TC2): c.2642A> T (p.Asn881Ile) single nucleotide variant Pathogenic rs80338930 GRCh38 Chromosome 5, 149027090: 149027090
29 SH3TC2 NM_024577.3(SH3TC2): c.2710C> T (p.Arg904Ter) single nucleotide variant Pathogenic rs80338931 GRCh37 Chromosome 5, 148406585: 148406585
30 SH3TC2 NM_024577.3(SH3TC2): c.2710C> T (p.Arg904Ter) single nucleotide variant Pathogenic rs80338931 GRCh38 Chromosome 5, 149027022: 149027022
31 SH3TC2 NM_024577.3(SH3TC2): c.28delG (p.Glu10Serfs) deletion Pathogenic rs80338918 GRCh37 Chromosome 5, 148442558: 148442558
32 SH3TC2 NM_024577.3(SH3TC2): c.28delG (p.Glu10Serfs) deletion Pathogenic rs80338918 GRCh38 Chromosome 5, 149062995: 149062995
33 SH3TC2 NM_024577.3(SH3TC2): c.3326G> C (p.Arg1109Pro) single nucleotide variant Pathogenic rs80338935 GRCh37 Chromosome 5, 148389834: 148389834
34 SH3TC2 NM_024577.3(SH3TC2): c.3326G> C (p.Arg1109Pro) single nucleotide variant Pathogenic rs80338935 GRCh38 Chromosome 5, 149010271: 149010271
35 SH3TC2 NM_024577.3(SH3TC2): c.3341delC (p.Pro1114Leufs) deletion Pathogenic rs80338936 GRCh37 Chromosome 5, 148388551: 148388551
36 SH3TC2 NM_024577.3(SH3TC2): c.3341delC (p.Pro1114Leufs) deletion Pathogenic rs80338936 GRCh38 Chromosome 5, 149008988: 149008988
37 SH3TC2 NM_024577.3(SH3TC2): c.3601C> T (p.Gln1201Ter) single nucleotide variant Pathogenic rs80338937 GRCh37 Chromosome 5, 148386518: 148386518
38 SH3TC2 NM_024577.3(SH3TC2): c.3601C> T (p.Gln1201Ter) single nucleotide variant Pathogenic rs80338937 GRCh38 Chromosome 5, 149006955: 149006955
39 SH3TC2 NM_024577.3(SH3TC2): c.920G> A (p.Trp307Ter) single nucleotide variant Pathogenic rs80338921 GRCh37 Chromosome 5, 148417939: 148417939
40 SH3TC2 NM_024577.3(SH3TC2): c.920G> A (p.Trp307Ter) single nucleotide variant Pathogenic rs80338921 GRCh38 Chromosome 5, 149038376: 149038376
41 SH3TC2 NM_024577.3(SH3TC2): c.1A> G (p.Met1Val) single nucleotide variant Likely pathogenic rs864309709 GRCh37 Chromosome 5, 148442585: 148442585
42 SH3TC2 NM_024577.3(SH3TC2): c.1A> G (p.Met1Val) single nucleotide variant Likely pathogenic rs864309709 GRCh38 Chromosome 5, 149063022: 149063022
43 SH3TC2 NM_024577.3(SH3TC2): c.820_821insT (p.Lys274Ilefs) insertion Pathogenic rs879253859 GRCh38 Chromosome 5, 149038475: 149038476
44 SH3TC2 NM_024577.3(SH3TC2): c.820_821insT (p.Lys274Ilefs) insertion Pathogenic rs879253859 GRCh37 Chromosome 5, 148418038: 148418039
45 SH3TC2 NM_024577.3(SH3TC2): c.3675+2dup duplication Pathogenic GRCh38 Chromosome 5, 149006879: 149006879
46 SH3TC2 NM_024577.3(SH3TC2): c.3675+2dup duplication Pathogenic GRCh37 Chromosome 5, 148386442: 148386442

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

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

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

Pathways related to Charcot-Marie-Tooth Disease, Type 4c according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.6 CREB1 RAB11A
2 10.24 CREB1 SOX10

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

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

# Name GO ID Score Top Affiliating Genes
1 recycling endosome GO:0055037 8.62 RAB11A SH3TC2

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

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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