CMTDIF
MCID: CHR484
MIFTS: 33

Charcot-Marie-Tooth Disease, Dominant Intermediate F (CMTDIF)

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

Aliases & Classifications for Charcot-Marie-Tooth Disease, Dominant Intermediate F

MalaCards integrated aliases for Charcot-Marie-Tooth Disease, Dominant Intermediate F:

Name: Charcot-Marie-Tooth Disease, Dominant Intermediate F 58 54 30 13 6 74
Cmtdif 58 12 54 60 76
Autosomal Dominant Intermediate Charcot-Marie-Tooth Disease Type F 12 54 60
Charcot-Marie-Tooth Disease Dominant Intermediate F 12 15
Charcot-Marie-Tooth Disease, Dominant, Intermediate Type, F 76
Charcot-Marie-Tooth Disease, Dominant Intermediate, Type F 41
Gnb4-Related Intermediate Charcot-Marie-Tooth Neuropathy 54
Di-Cmtf 54

Characteristics:

Orphanet epidemiological data:

60
autosomal dominant intermediate charcot-marie-tooth disease type f
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: All ages;

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
slowly progressive
males are more severely affected than females
onset around adolescence in males
later onset in females
one chinese family and 1 unrelated patient have been reported (last curated april 2013)


HPO:

33
charcot-marie-tooth disease, dominant intermediate f:
Onset and clinical course slow progression
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 60  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0110206
OMIM 58 615185
MeSH 45 D002607
ICD10 34 G60.0
ICD10 via Orphanet 35 G60.0
Orphanet 60 ORPHA352670
UMLS 74 C3554654

Summaries for Charcot-Marie-Tooth Disease, Dominant Intermediate F

UniProtKB/Swiss-Prot : 76 Charcot-Marie-Tooth disease, dominant, intermediate type, F: A 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. CMTDIF is characterized by onset around adolescence of slowly progressive distal muscle atrophy and weakness affecting the upper and lower limbs and resulting in steppage gait. There is distal sensory impairment with decreased reflexes. Nerve conduction velocities are variable, ranging from the demyelinating to the axonal range.

MalaCards based summary : Charcot-Marie-Tooth Disease, Dominant Intermediate F, also known as cmtdif, is related to brachydactyly, type e2 and maturity-onset diabetes of the young, type 7. An important gene associated with Charcot-Marie-Tooth Disease, Dominant Intermediate F is GNB4 (G Protein Subunit Beta 4), and among its related pathways/superpathways are Activation of cAMP-Dependent PKA and TGF-Beta Pathway. Related phenotypes are pes cavus and hyporeflexia

Disease Ontology : 12 A Charcot-Marie-Tooth disease intermediate type that has material basis in heterozygous mutation in the GNB4 gene on chromosome 3q28.

OMIM : 58 CMTDIF is an autosomal dominant neurologic disorder characterized by onset around adolescence of slowly progressive distal muscle atrophy and weakness affecting the upper and lower limbs and resulting in steppage gait. There is distal sensory impairment with decreased reflexes. Nerve conduction velocities are variable, ranging from the demyelinating to the axonal range (summary by Soong et al., 2013). For a discussion of genetic heterogeneity of CMTDI, see 606482. (615185)

Related Diseases for Charcot-Marie-Tooth Disease, Dominant Intermediate F

Diseases in the Charcot-Marie-Tooth Disease, Dominant Intermediate D family:

Charcot-Marie-Tooth Disease, Dominant Intermediate E Charcot-Marie-Tooth Disease, Dominant Intermediate F
Charcot-Marie-Tooth Disease, Recessive Intermediate D Charcot-Marie-Tooth Disease, Dominant Intermediate G

Diseases related to Charcot-Marie-Tooth Disease, Dominant Intermediate F via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 brachydactyly, type e2 9.7 GNA11 GNA15
2 maturity-onset diabetes of the young, type 7 9.6 GNA11 GNA15
3 dyschromatosis universalis hereditaria 9.5 GNA11 GNA15

Symptoms & Phenotypes for Charcot-Marie-Tooth Disease, Dominant Intermediate F

Human phenotypes related to Charcot-Marie-Tooth Disease, Dominant Intermediate F:

33 (show all 7)
# Description HPO Frequency HPO Source Accession
1 pes cavus 33 HP:0001761
2 hyporeflexia 33 HP:0001265
3 hammertoe 33 HP:0001765
4 steppage gait 33 HP:0003376
5 distal sensory impairment 33 HP:0002936
6 onion bulb formation 33 HP:0003383
7 axonal regeneration 33 HP:0003450

Symptoms via clinical synopsis from OMIM:

58
Skeletal Feet:
pes cavus
hammertoes

Neurologic Peripheral Nervous System:
hyporeflexia
steppage gait
distal sensory impairment
onion bulb formation
sural nerve biopsy shows loss of myelinated fibers
more

Clinical features from OMIM:

615185

Drugs & Therapeutics for Charcot-Marie-Tooth Disease, Dominant Intermediate F

Search Clinical Trials , NIH Clinical Center for Charcot-Marie-Tooth Disease, Dominant Intermediate F

Genetic Tests for Charcot-Marie-Tooth Disease, Dominant Intermediate F

Genetic tests related to Charcot-Marie-Tooth Disease, Dominant Intermediate F:

# Genetic test Affiliating Genes
1 Charcot-Marie-Tooth Disease, Dominant Intermediate F 30 GNB4

Anatomical Context for Charcot-Marie-Tooth Disease, Dominant Intermediate F

Publications for Charcot-Marie-Tooth Disease, Dominant Intermediate F

Articles related to Charcot-Marie-Tooth Disease, Dominant Intermediate F:

# Title Authors Year
1
Exome sequencing identifies GNB4 mutations as a cause of dominant intermediate Charcot-Marie-Tooth disease. ( 23434117 )
2013

Variations for Charcot-Marie-Tooth Disease, Dominant Intermediate F

UniProtKB/Swiss-Prot genetic disease variations for Charcot-Marie-Tooth Disease, Dominant Intermediate F:

76
# Symbol AA change Variation ID SNP ID
1 GNB4 p.Gly53Asp VAR_069908 rs387907340
2 GNB4 p.Lys89Glu VAR_069909 rs387907341

ClinVar genetic disease variations for Charcot-Marie-Tooth Disease, Dominant Intermediate F:

6 (show top 50) (show all 68)
# Gene Variation Type Significance SNP ID Assembly Location
1 GNB4 NM_021629.3(GNB4): c.158G> A (p.Gly53Asp) single nucleotide variant Pathogenic rs387907340 GRCh37 Chromosome 3, 179137232: 179137232
2 GNB4 NM_021629.3(GNB4): c.158G> A (p.Gly53Asp) single nucleotide variant Pathogenic rs387907340 GRCh38 Chromosome 3, 179419444: 179419444
3 GNB4 NM_021629.3(GNB4): c.265A> G (p.Lys89Glu) single nucleotide variant Pathogenic rs387907341 GRCh37 Chromosome 3, 179134283: 179134283
4 GNB4 NM_021629.3(GNB4): c.265A> G (p.Lys89Glu) single nucleotide variant Pathogenic rs387907341 GRCh38 Chromosome 3, 179416495: 179416495
5 GNB4 NM_021629.3(GNB4): c.196G> A (p.Asp66Asn) single nucleotide variant Uncertain significance rs864622729 GRCh37 Chromosome 3, 179137194: 179137194
6 GNB4 NM_021629.3(GNB4): c.196G> A (p.Asp66Asn) single nucleotide variant Uncertain significance rs864622729 GRCh38 Chromosome 3, 179419406: 179419406
7 GNB4 NM_021629.3(GNB4): c.771A> G (p.Ala257=) single nucleotide variant Likely benign rs878855069 GRCh38 Chromosome 3, 179405335: 179405335
8 GNB4 NM_021629.3(GNB4): c.771A> G (p.Ala257=) single nucleotide variant Likely benign rs878855069 GRCh37 Chromosome 3, 179123123: 179123123
9 GNB4 NM_021629.3(GNB4): c.958G> A (p.Val320Ile) single nucleotide variant Benign rs61750380 GRCh37 Chromosome 3, 179119066: 179119066
10 GNB4 NM_021629.3(GNB4): c.958G> A (p.Val320Ile) single nucleotide variant Benign rs61750380 GRCh38 Chromosome 3, 179401278: 179401278
11 GNB4 NM_021629.3(GNB4): c.84A> C (p.Ala28=) single nucleotide variant Likely benign rs770125763 GRCh37 Chromosome 3, 179138689: 179138689
12 GNB4 NM_021629.3(GNB4): c.84A> C (p.Ala28=) single nucleotide variant Likely benign rs770125763 GRCh38 Chromosome 3, 179420901: 179420901
13 GNB4 NM_021629.3(GNB4): c.58-8dupT duplication Benign rs112500963 GRCh37 Chromosome 3, 179138723: 179138723
14 GNB4 NM_021629.3(GNB4): c.58-8dupT duplication Benign rs112500963 GRCh38 Chromosome 3, 179420935: 179420935
15 GNB4 NM_021629.3(GNB4): c.48T> C (p.Asn16=) single nucleotide variant Benign rs1078749 GRCh37 Chromosome 3, 179143941: 179143941
16 GNB4 NM_021629.3(GNB4): c.48T> C (p.Asn16=) single nucleotide variant Benign rs1078749 GRCh38 Chromosome 3, 179426153: 179426153
17 GNB4 NM_021629.3(GNB4): c.848G> C (p.Arg283Pro) single nucleotide variant Uncertain significance rs186593898 GRCh38 Chromosome 3, 179405258: 179405258
18 GNB4 NM_021629.3(GNB4): c.848G> C (p.Arg283Pro) single nucleotide variant Uncertain significance rs186593898 GRCh37 Chromosome 3, 179123046: 179123046
19 GNB4 NM_021629.3(GNB4): c.186T> C (p.His62=) single nucleotide variant Benign rs149798652 GRCh37 Chromosome 3, 179137204: 179137204
20 GNB4 NM_021629.3(GNB4): c.186T> C (p.His62=) single nucleotide variant Benign rs149798652 GRCh38 Chromosome 3, 179419416: 179419416
21 GNB4 NC_000003.12: g.(?_179401193)_(179426220_?)dup duplication Uncertain significance GRCh38 Chromosome 3, 179401193: 179426220
22 GNB4 NC_000003.12: g.(?_179401193)_(179426220_?)dup duplication Uncertain significance GRCh37 Chromosome 3, 179118981: 179144008
23 GNB4 NM_021629.3(GNB4): c.799G> A (p.Asp267Asn) single nucleotide variant Uncertain significance rs752762550 GRCh38 Chromosome 3, 179405307: 179405307
24 GNB4 NM_021629.3(GNB4): c.799G> A (p.Asp267Asn) single nucleotide variant Uncertain significance rs752762550 GRCh37 Chromosome 3, 179123095: 179123095
25 GNB4 NM_021629.3(GNB4): c.195C> T (p.Tyr65=) single nucleotide variant Likely benign rs768164095 GRCh38 Chromosome 3, 179419407: 179419407
26 GNB4 NM_021629.3(GNB4): c.195C> T (p.Tyr65=) single nucleotide variant Likely benign rs768164095 GRCh37 Chromosome 3, 179137195: 179137195
27 GNB4 NM_021629.3(GNB4): c.96+9T> C single nucleotide variant Likely benign rs1222924595 GRCh37 Chromosome 3, 179138668: 179138668
28 GNB4 NM_021629.3(GNB4): c.96+9T> C single nucleotide variant Likely benign rs1222924595 GRCh38 Chromosome 3, 179420880: 179420880
29 GNB4 NM_021629.3(GNB4): c.27A> G (p.Gln9=) single nucleotide variant Likely benign rs376598495 GRCh38 Chromosome 3, 179426174: 179426174
30 GNB4 NM_021629.3(GNB4): c.27A> G (p.Gln9=) single nucleotide variant Likely benign rs376598495 GRCh37 Chromosome 3, 179143962: 179143962
31 GNB4 NM_021629.3(GNB4): c.853T> G (p.Leu285Val) single nucleotide variant Uncertain significance rs554623238 GRCh38 Chromosome 3, 179405253: 179405253
32 GNB4 NM_021629.3(GNB4): c.853T> G (p.Leu285Val) single nucleotide variant Uncertain significance rs554623238 GRCh37 Chromosome 3, 179123041: 179123041
33 GNB4 NM_021629.3(GNB4): c.916+9A> G single nucleotide variant Likely benign rs376068792 GRCh38 Chromosome 3, 179405181: 179405181
34 GNB4 NM_021629.3(GNB4): c.916+9A> G single nucleotide variant Likely benign rs376068792 GRCh37 Chromosome 3, 179122969: 179122969
35 GNB4 NM_021629.3(GNB4): c.229G> A (p.Gly77Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs1553851490 GRCh37 Chromosome 3, 179134319: 179134319
36 GNB4 NM_021629.3(GNB4): c.229G> A (p.Gly77Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs1553851490 GRCh38 Chromosome 3, 179416531: 179416531
37 GNB4 NM_021629.3(GNB4): c.917-4delT deletion Benign rs764075662 GRCh38 Chromosome 3, 179401323: 179401323
38 GNB4 NM_021629.3(GNB4): c.917-4delT deletion Benign rs764075662 GRCh37 Chromosome 3, 179119111: 179119111
39 GNB4 NM_021629.3(GNB4): c.243T> C (p.Ile81=) single nucleotide variant Benign rs200696108 GRCh38 Chromosome 3, 179416517: 179416517
40 GNB4 NM_021629.3(GNB4): c.243T> C (p.Ile81=) single nucleotide variant Benign rs200696108 GRCh37 Chromosome 3, 179134305: 179134305
41 GNB4 NM_021629.3(GNB4): c.903A> T (p.Lys301Asn) single nucleotide variant Uncertain significance rs1167931862 GRCh37 Chromosome 3, 179122991: 179122991
42 GNB4 NM_021629.3(GNB4): c.903A> T (p.Lys301Asn) single nucleotide variant Uncertain significance rs1167931862 GRCh38 Chromosome 3, 179405203: 179405203
43 GNB4 NM_021629.3(GNB4): c.204-4C> G single nucleotide variant Likely benign rs377746889 GRCh38 Chromosome 3, 179416560: 179416560
44 GNB4 NM_021629.3(GNB4): c.204-4C> G single nucleotide variant Likely benign rs377746889 GRCh37 Chromosome 3, 179134348: 179134348
45 GNB4 NM_021629.3(GNB4): c.699+10T> C single nucleotide variant Likely benign rs1433602623 GRCh38 Chromosome 3, 179413402: 179413402
46 GNB4 NM_021629.3(GNB4): c.699+10T> C single nucleotide variant Likely benign rs1433602623 GRCh37 Chromosome 3, 179131190: 179131190
47 GNB4 NM_021629.3(GNB4): c.596T> A (p.Phe199Tyr) single nucleotide variant Uncertain significance GRCh38 Chromosome 3, 179413515: 179413515
48 GNB4 NM_021629.3(GNB4): c.596T> A (p.Phe199Tyr) single nucleotide variant Uncertain significance GRCh37 Chromosome 3, 179131303: 179131303
49 GNB4 NM_021629.3(GNB4): c.44G> A (p.Arg15Gln) single nucleotide variant Uncertain significance GRCh37 Chromosome 3, 179143945: 179143945
50 GNB4 NM_021629.3(GNB4): c.44G> A (p.Arg15Gln) single nucleotide variant Uncertain significance GRCh38 Chromosome 3, 179426157: 179426157

Expression for Charcot-Marie-Tooth Disease, Dominant Intermediate F

Search GEO for disease gene expression data for Charcot-Marie-Tooth Disease, Dominant Intermediate F.

Pathways for Charcot-Marie-Tooth Disease, Dominant Intermediate F

Pathways related to Charcot-Marie-Tooth Disease, Dominant Intermediate F according to GeneCards Suite gene sharing:

(show all 45)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.12 GNA11 GNA15 GNB4
2
Show member pathways
13.1 GNA11 GNA15 GNB4
3
Show member pathways
13.01 GNA11 GNA15 GNB4
4
Show member pathways
13 GNA11 GNA15 GNB4
5
Show member pathways
12.94 GNA11 GNA15 GNB4
6
Show member pathways
12.93 GNA11 GNA15 GNB4
7
Show member pathways
12.74 GNA11 GNA15 GNB4
8
Show member pathways
12.71 GNA11 GNA15 GNB4
9
Show member pathways
12.71 GNA11 GNA15 GNB4
10
Show member pathways
12.7 GNA11 GNA15 GNB4
11
Show member pathways
12.67 GNA11 GNA15 GNB4
12
Show member pathways
12.67 GNA11 GNA15 GNB4
13
Show member pathways
12.66 GNA11 GNA15 GNB4
14
Show member pathways
12.63 GNA11 GNA15 GNB4
15
Show member pathways
12.53 GNA11 GNA15 GNB4
16
Show member pathways
12.5 GNA11 GNA15 GNB4
17
Show member pathways
12.44 GNA11 GNA15 GNB4
18
Show member pathways
12.31 GNA11 GNA15 GNB4
19
Show member pathways
12.22 GNA11 GNA15 GNB4
20
Show member pathways
12.19 GNA11 GNB4
21
Show member pathways
12.11 GNA11 GNA15 GNB4
22
Show member pathways
12.05 GNA15 GNB4
23 12.05 GNA11 GNA15 GNB4
24
Show member pathways
11.96 GNA11 GNA15
25
Show member pathways
11.96 GNA11 GNA15 GNB4
26
Show member pathways
11.91 GNA11 GNA15 GNB4
27
Show member pathways
11.91 GNA11 GNA15 GNB4
28
Show member pathways
11.87 GNA11 GNA15 GNB4
29
Show member pathways
11.83 GNA11 GNA15 GNB4
30
Show member pathways
11.72 GNA11 GNA15
31
Show member pathways
11.67 GNA11 GNA15 GNB4
32 11.64 GNA11 GNA15
33 11.64 GNA11 GNA15
34
Show member pathways
11.64 GNA11 GNA15 GNB4
35
Show member pathways
11.54 GNA11 GNA15 GNB4
36 11.42 GNA11 GNA15
37 11.38 GNA11 GNA15 GNB4
38 11.31 GNA11 GNA15
39 11.29 GNA11 GNB4
40
Show member pathways
11.21 GNA11 GNA15 GNB4
41 11.09 GNA11 GNA15
42 11.03 GNA11 GNA15
43 11.01 GNA11 GNA15 GNB4
44 10.66 GNA11 GNA15 GNB4
45 10.48 GNA11 GNA15 GNB4

GO Terms for Charcot-Marie-Tooth Disease, Dominant Intermediate F

Cellular components related to Charcot-Marie-Tooth Disease, Dominant Intermediate F according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lysosomal membrane GO:0005765 8.96 GNA11 GNB4
2 heterotrimeric G-protein complex GO:0005834 8.62 GNA11 GNA15

Biological processes related to Charcot-Marie-Tooth Disease, Dominant Intermediate F according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 signal transduction GO:0007165 9.43 GNA11 GNA15 GNB4
2 platelet activation GO:0030168 9.16 GNA11 GNA15
3 adenylate cyclase-modulating G protein-coupled receptor signaling pathway GO:0007188 8.96 GNA11 GNA15
4 phospholipase C-activating dopamine receptor signaling pathway GO:0060158 8.62 GNA11 GNA15

Molecular functions related to Charcot-Marie-Tooth Disease, Dominant Intermediate F according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 GTPase activity GO:0003924 9.26 GNA11 GNA15
2 G protein-coupled receptor binding GO:0001664 9.16 GNA11 GNA15
3 G-protein beta/gamma-subunit complex binding GO:0031683 8.96 GNA11 GNA15
4 guanyl nucleotide binding GO:0019001 8.62 GNA11 GNA15

Sources for Charcot-Marie-Tooth Disease, Dominant Intermediate F

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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