CMT4H
MCID: CHR421
MIFTS: 37

Charcot-Marie-Tooth Disease, Type 4h (CMT4H)

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

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

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

Name: Charcot-Marie-Tooth Disease, Type 4h 58 54 30 13 6 41 74
Cmt4h 58 12 25 54 60 76
Charcot-Marie-Tooth Disease Type 4h 12 25 54 60 15
Charcot-Marie-Tooth Neuropathy Type 4h 12 25 76
Charcot-Marie-Tooth Disease, Demyelinating, Autosomal Recessive, Type 4h 58 54
Charcot-Marie-Tooth Disease, Autosomal Recessive, Type 4h 58 54
Charcot-Marie-Tooth Neuropathy, Type 4h 58 54
Autosomal Recessive Demyelinating Charcot-Marie-Tooth Disease Type 4h 12
Charcot-Marie-Tooth Disease Demyelinating Autosomal Recessive 4h 76
Autosomal Recessive Charcot-Marie-Tooth Disease Type 4h 12
Charcot-Marie-Tooth Disease 4h 76

Characteristics:

Orphanet epidemiological data:

60
charcot-marie-tooth disease type 4h
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
usually begins in feet and legs (peroneal distribution)
onset before age 2 years
severe disorder
genetic heterogeneity (see cmt4a )


HPO:

33
charcot-marie-tooth disease, type 4h:
Onset and clinical course infantile onset
Inheritance heterogeneous autosomal recessive inheritance


Classifications:

Orphanet: 60  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0110192
OMIM 58 609311
MeSH 45 D002607
ICD10 34 G60.0
ICD10 via Orphanet 35 G60.0
UMLS via Orphanet 75 C1836336
Orphanet 60 ORPHA99954
MedGen 43 C1836336
UMLS 74 C1836336

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

UniProtKB/Swiss-Prot : 76 Charcot-Marie-Tooth disease 4H: 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.

MalaCards based summary : Charcot-Marie-Tooth Disease, Type 4h, also known as cmt4h, is related to neuropathy, congenital hypomyelinating, 1, autosomal recessive and charcot-marie-tooth disease, and has symptoms including waddling gait An important gene associated with Charcot-Marie-Tooth Disease, Type 4h is FGD4 (FYVE, RhoGEF And PH Domain Containing 4), and among its related pathways/superpathways are Signaling by Rho GTPases and MAPK-Erk Pathway. Related phenotypes are scoliosis and pes cavus

Disease Ontology : 12 A Charcot-Marie-Tooth disease type 4 that has material basis in mutations in the gene encoding frabin (FGD4).

Description from OMIM: 609311
GeneReviews: NBK153601

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

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 Type X
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 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 4h via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 neuropathy, congenital hypomyelinating, 1, autosomal recessive 11.3
2 charcot-marie-tooth disease 10.8
3 tooth disease 10.8
4 neuropathy 10.1

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

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

33 (show all 15)
# Description HPO Frequency HPO Source Accession
1 scoliosis 33 HP:0002650
2 pes cavus 33 HP:0001761
3 decreased motor nerve conduction velocity 33 HP:0003431
4 waddling gait 33 HP:0002515
5 motor delay 33 HP:0001270
6 talipes equinovarus 33 HP:0001762
7 areflexia 33 HP:0001284
8 hyporeflexia 33 HP:0001265
9 upper limb muscle weakness 33 HP:0003484
10 distal lower limb muscle weakness 33 HP:0009053
11 peripheral demyelination 33 HP:0011096
12 distal sensory impairment 33 HP:0002936
13 distal lower limb amyotrophy 33 HP:0008944
14 decreased number of peripheral myelinated nerve fibers 33 HP:0003380
15 onion bulb formation 33 HP:0003383

Symptoms via clinical synopsis from OMIM:

58
Skeletal Spine:
scoliosis

Neurologic Peripheral Nervous System:
areflexia
hyporeflexia
distal sensory impairment
delayed motor development
decreased motor nerve conduction velocity (ncv) (less than 38 m/s)
more
Skeletal Feet:
pes cavus
pes equinus

Clinical features from OMIM:

609311

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


waddling gait

GenomeRNAi Phenotypes related to Charcot-Marie-Tooth Disease, Type 4h according to GeneCards Suite gene sharing:

27 (show all 12)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-101 9.4 FGD4
2 Increased shRNA abundance (Z-score > 2) GR00366-A-103 9.4 FGD4
3 Increased shRNA abundance (Z-score > 2) GR00366-A-121 9.4 FGD4
4 Increased shRNA abundance (Z-score > 2) GR00366-A-125 9.4 FGD4
5 Increased shRNA abundance (Z-score > 2) GR00366-A-140 9.4 ARHGEF3 FGD4
6 Increased shRNA abundance (Z-score > 2) GR00366-A-149 9.4 FGD4
7 Increased shRNA abundance (Z-score > 2) GR00366-A-205 9.4 FGD4
8 Increased shRNA abundance (Z-score > 2) GR00366-A-214 9.4 ARHGEF3
9 Increased shRNA abundance (Z-score > 2) GR00366-A-42 9.4 ARHGEF3
10 Increased shRNA abundance (Z-score > 2) GR00366-A-56 9.4 FGD4
11 Increased shRNA abundance (Z-score > 2) GR00366-A-92 9.4 FGD4
12 Decreased focal adhesion (FA) area, decreased FA length, decreased FA mean intensity, increased number of small and round FAs, increased FA abundance GR00210-A 8.96 ARHGEF3 CDC42

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

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

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

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

# Genetic test Affiliating Genes
1 Charcot-Marie-Tooth Disease, Type 4h 30 FGD4

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

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

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

# Title Authors Year
1
A novel mutation in FGD4 causes Charcot-Marie-Tooth disease type 4H with cranial nerve involvement. ( 28847448 )
2017
2
Charcot-Marie-Tooth Disease Type 4H Resulting from Compound Heterozygous Mutations in FGD4 from Nonconsanguineous Korean Families. ( 26400421 )
2015
3
A novel mutation in FGD4/FRABIN causes Charcot Marie Tooth disease type 4H in patients from a consanguineous Tunisian family. ( 23550889 )
2013
4
The first Japanese case of Charcot-Marie-Tooth disease type 4H with a novel FGD4 c.837-1G>A mutation. ( 23770104 )
2013
5
Two novel missense mutations in FGD4/FRABIN cause Charcot-Marie-Tooth type 4H (CMT4H). ( 22734899 )
2012
6
Further evidence that mutations in FGD4/frabin cause Charcot-Marie-Tooth disease type 4H. ( 19332693 )
2009
7
A novel Frabin (FGD4) nonsense mutation p.R275X associated with phenotypic variability in CMT4H. ( 19221294 )
2009
8
Peripheral nerve demyelination caused by a mutant Rho GTPase guanine nucleotide exchange factor, frabin/FGD4. ( 17564972 )
2007
9
Mutations in FGD4 encoding the Rho GDP/GTP exchange factor FRABIN cause autosomal recessive Charcot-Marie-Tooth type 4H. ( 17564959 )
2007
10
Homozygosity mapping of autosomal recessive demyelinating Charcot-Marie-Tooth neuropathy (CMT4H) to a novel locus on chromosome 12p11.21-q13.11. ( 15744041 )
2005

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

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

76
# Symbol AA change Variation ID SNP ID
1 FGD4 p.Met298Arg VAR_034957 rs63749871
2 FGD4 p.Met298Thr VAR_044321 rs63749871

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

6 (show all 28)
# Gene Variation Type Significance SNP ID Assembly Location
1 FGD4 NM_139241.3(FGD4): c.1305G> A (p.Arg435=) single nucleotide variant Benign rs10844253 GRCh37 Chromosome 12, 32764184: 32764184
2 FGD4 NM_139241.3(FGD4): c.1305G> A (p.Arg435=) single nucleotide variant Benign rs10844253 GRCh38 Chromosome 12, 32611250: 32611250
3 FGD4 NM_139241.3(FGD4): c.1518G> A (p.Ala506=) single nucleotide variant Benign rs11052110 GRCh37 Chromosome 12, 32777362: 32777362
4 FGD4 NM_139241.3(FGD4): c.1518G> A (p.Ala506=) single nucleotide variant Benign rs11052110 GRCh38 Chromosome 12, 32624428: 32624428
5 FGD4 GRCh37/hg19 12p11.21(chr12: 32717818-32778686)x4 copy number gain Likely pathogenic GRCh37 Chromosome 12, 32711272: 32788014
6 FGD4 NM_139241.3(FGD4): c.956G> A (p.Arg319His) single nucleotide variant Uncertain significance GRCh38 Chromosome 12, 32602280: 32602280
7 FGD4 NM_139241.3(FGD4): c.956G> A (p.Arg319His) single nucleotide variant Uncertain significance GRCh37 Chromosome 12, 32755214: 32755214
8 FGD4 NM_001304481.1(FGD4): c.3delG (p.Gly3Alafs) deletion Uncertain significance GRCh37 Chromosome 12, 32639070: 32639070
9 FGD4 NM_001304481.1(FGD4): c.3delG (p.Gly3Alafs) deletion Uncertain significance GRCh38 Chromosome 12, 32486136: 32486136
10 FGD4 NM_139241.3(FGD4): c.893T> G (p.Met298Arg) single nucleotide variant Likely pathogenic rs63749871 GRCh38 Chromosome 12, 32602217: 32602217
11 FGD4 NM_139241.3(FGD4): c.893T> G (p.Met298Arg) single nucleotide variant Likely pathogenic rs63749871 GRCh37 Chromosome 12, 32755151: 32755151
12 FGD4 NM_139241.2(FGD4): c.1698G> H single nucleotide variant Pathogenic rs281865064 GRCh38 Chromosome 12, 32625716: 32625716
13 FGD4 NM_139241.2(FGD4): c.1698G> H single nucleotide variant Pathogenic rs281865064 GRCh37 Chromosome 12, 32778650: 32778650
14 FGD4 NM_139241.3(FGD4): c.1325G> A (p.Arg442His) single nucleotide variant Pathogenic rs281865063 GRCh38 Chromosome 12, 32611270: 32611270
15 FGD4 NM_139241.3(FGD4): c.1325G> A (p.Arg442His) single nucleotide variant Pathogenic rs281865063 GRCh37 Chromosome 12, 32764204: 32764204
16 FGD4 NM_139241.3(FGD4): c.1762-2A> G single nucleotide variant Pathogenic rs281865065 GRCh38 Chromosome 12, 32633547: 32633547
17 FGD4 NM_139241.3(FGD4): c.1762-2A> G single nucleotide variant Pathogenic rs281865065 GRCh37 Chromosome 12, 32786481: 32786481
18 FGD4 NM_139241.3(FGD4): c.823C> T (p.Arg275Ter) single nucleotide variant Pathogenic rs118203974 GRCh38 Chromosome 12, 32601410: 32601410
19 FGD4 NM_139241.3(FGD4): c.823C> T (p.Arg275Ter) single nucleotide variant Pathogenic rs118203974 GRCh37 Chromosome 12, 32754344: 32754344
20 FGD4 NM_139241.3(FGD4): c.893T> C (p.Met298Thr) single nucleotide variant Pathogenic rs63749871 GRCh38 Chromosome 12, 32602217: 32602217
21 FGD4 NM_139241.3(FGD4): c.893T> C (p.Met298Thr) single nucleotide variant Pathogenic rs63749871 GRCh37 Chromosome 12, 32755151: 32755151
22 FGD4 NM_139241.3(FGD4): c.1756G> T (p.Gly586Ter) single nucleotide variant Pathogenic rs118203973 GRCh38 Chromosome 12, 32625774: 32625774
23 FGD4 NM_139241.3(FGD4): c.1756G> T (p.Gly586Ter) single nucleotide variant Pathogenic rs118203973 GRCh37 Chromosome 12, 32778708: 32778708
24 FGD4 NM_001304480.1(FGD4): c.1964_1965del (p.Glu655Glyfs) deletion Pathogenic GRCh37 Chromosome 12, 32777995: 32777996
25 FGD4 NM_001304480.1(FGD4): c.1964_1965del (p.Glu655Glyfs) deletion Pathogenic GRCh38 Chromosome 12, 32625061: 32625062
26 FGD4 FGD4, 893T-G single nucleotide variant Pathogenic
27 FGD4 NM_139241.3(FGD4): c.670C> T (p.Arg224Ter) single nucleotide variant Pathogenic rs118203972 GRCh38 Chromosome 12, 32598566: 32598566
28 FGD4 NM_139241.3(FGD4): c.670C> T (p.Arg224Ter) single nucleotide variant Pathogenic rs118203972 GRCh37 Chromosome 12, 32751500: 32751500

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

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

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

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

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.29 ARHGEF3 CDC42 FGD4
2
Show member pathways
12.18 ARHGEF3 CDC42
3
Show member pathways
12.09 ARHGEF3 CDC42 FGD4
4
Show member pathways
11.81 ARHGEF3 CDC42
5
Show member pathways
11.77 ARHGEF3 CDC42
6 11.39 ARHGEF3 CDC42
7 10.95 ARHGEF3 CDC42
8 10.64 ARHGEF3 CDC42
9 10.51 ARHGEF3 CDC42
10 10.13 CDC42 FGD4

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

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

# Name GO ID Score Top Affiliating Genes
1 filopodium GO:0030175 8.62 CDC42 FGD4

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

# Name GO ID Score Top Affiliating Genes
1 positive regulation of apoptotic process GO:0043065 9.37 ARHGEF3 FGD4
2 actin cytoskeleton organization GO:0030036 9.32 CDC42 FGD4
3 regulation of cell shape GO:0008360 9.26 CDC42 FGD4
4 regulation of Rho protein signal transduction GO:0035023 9.16 ARHGEF3 FGD4
5 Rho protein signal transduction GO:0007266 8.96 ARHGEF3 CDC42
6 regulation of small GTPase mediated signal transduction GO:0051056 8.8 ARHGEF3 CDC42 FGD4

Molecular functions related to Charcot-Marie-Tooth Disease, Type 4h according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 guanyl-nucleotide exchange factor activity GO:0005085 8.65 FGD4
2 Rho guanyl-nucleotide exchange factor activity GO:0005089 8.62 ARHGEF3 FGD4

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

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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