CMT4B3
MCID: CHR504
MIFTS: 35

Charcot-Marie-Tooth Disease, Type 4b3 (CMT4B3)

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

Aliases & Classifications for Charcot-Marie-Tooth Disease, Type 4b3

MalaCards integrated aliases for Charcot-Marie-Tooth Disease, Type 4b3:

Name: Charcot-Marie-Tooth Disease, Type 4b3 58 30 6 41 74
Cmt4b3 58 12 60 76
Charcot-Marie-Tooth Disease Type 4b3 12 60 15
Charcot-Marie-Tooth Disease with Focally Folded Myelin 60
Charcot-Marie-Tooth Neuropathy Type 4b3 76
Charcot-Marie-Tooth Disease 4b3 76

Characteristics:

Orphanet epidemiological data:

60
charcot-marie-tooth disease type 4b3
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
two families have been reported (last curated december 2014)
onset between 5 and 20 years
patients may become wheelchair-bound as adults
one consanguineous saudi family had additional features of microcephaly, mental retardation, ophthalmoplegia, and syndactyly


HPO:

33
charcot-marie-tooth disease, type 4b3:
Onset and clinical course progressive
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 60  
Rare neurological diseases


Summaries for Charcot-Marie-Tooth Disease, Type 4b3

UniProtKB/Swiss-Prot : 76 Charcot-Marie-Tooth disease 4B3: 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 4b3, also known as cmt4b3, is related to charcot-marie-tooth disease, demyelinating, type 1a and charcot-marie-tooth disease, type 4b2. An important gene associated with Charcot-Marie-Tooth Disease, Type 4b3 is SBF1 (SET Binding Factor 1), and among its related pathways/superpathways is RAB GEFs exchange GTP for GDP on RABs. Affiliated tissues include brain, and related phenotypes are brain atrophy and intellectual disability

Disease Ontology : 12 A Charcot-Marie-Tooth disease type 4 that has material basis in homozygous or compound heterozygous mutation in the SBF1 gene on chromosome 22q.

Description from OMIM: 615284

Related Diseases for Charcot-Marie-Tooth Disease, Type 4b3

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 4b3 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 19)
# Related Disease Score Top Affiliating Genes
1 charcot-marie-tooth disease, demyelinating, type 1a 32.5 GDAP1 MTMR2
2 charcot-marie-tooth disease, type 4b2 31.8 GDAP1 MTMR2 SBF1 SBF2
3 charcot-marie-tooth disease, type 4b1 31.5 GDAP1 MTMR2 SBF1 SBF2
4 charcot-marie-tooth disease 29.8 GDAP1 MTMR2 SBF1 SBF2
5 tooth disease 29.8 GDAP1 MTMR2 SBF1 SBF2
6 charcot-marie-tooth disease, demyelinating, type 1b 11.8
7 neuropathy, hereditary, with liability to pressure palsies 9.9 GDAP1 MTMR2
8 charcot-marie-tooth disease and deafness 9.9 GDAP1 MTMR2
9 neuropathy 9.8 GDAP1 SBF2
10 centronuclear myopathy 9.8 MTMR2 SBF1
11 hypertrophic neuropathy of dejerine-sottas 9.8 GDAP1 MTMR2
12 spinocerebellar ataxia type 1 with axonal neuropathy 9.7 MTMR2 SBF2
13 charcot-marie-tooth disease, type 4j 9.7 MTMR2 SBF2
14 sensory peripheral neuropathy 9.7 GDAP1 MTMR2
15 peripheral nervous system disease 9.6 GDAP1 MTMR2
16 early-onset glaucoma 9.5 MTMR2 SBF1 SBF2
17 charcot-marie-tooth disease, demyelinating, type 4f 9.5 GDAP1 MTMR2 SBF2
18 charcot-marie-tooth disease, type 4a 9.5 GDAP1 MTMR2 SBF2
19 charcot-marie-tooth disease, axonal, type 2e 9.5 GDAP1 MTMR2 SBF2

Graphical network of the top 20 diseases related to Charcot-Marie-Tooth Disease, Type 4b3:



Diseases related to Charcot-Marie-Tooth Disease, Type 4b3

Symptoms & Phenotypes for Charcot-Marie-Tooth Disease, Type 4b3

Human phenotypes related to Charcot-Marie-Tooth Disease, Type 4b3:

33 (show all 15)
# Description HPO Frequency HPO Source Accession
1 brain atrophy 33 occasional (7.5%) HP:0012444
2 intellectual disability 33 occasional (7.5%) HP:0001249
3 strabismus 33 occasional (7.5%) HP:0000486
4 ophthalmoplegia 33 occasional (7.5%) HP:0000602
5 urinary incontinence 33 occasional (7.5%) HP:0000020
6 syndactyly 33 occasional (7.5%) HP:0001159
7 gait disturbance 33 HP:0001288
8 scoliosis 33 HP:0002650
9 pes planus 33 HP:0001763
10 microcephaly 33 HP:0000252
11 decreased nerve conduction velocity 33 HP:0000762
12 areflexia 33 HP:0001284
13 limb muscle weakness 33 HP:0003690
14 distal sensory impairment 33 HP:0002936
15 onion bulb formation 33 HP:0003383

Symptoms via clinical synopsis from OMIM:

58
Skeletal Spine:
scoliosis

Neurologic Central Nervous System:
mental retardation (1 family)
brain atrophy (1 family)

Muscle Soft Tissue:
fiber-type grouping
distal limb muscle atrophy, lower more than upper
distal limb muscle weakness, lower more than upper
proximal muscles may be mildly affected
muscle biopsy shows neurogenic angulated fibers

Head And Neck Eyes:
strabismus (1 family)
ophthalmoplegia (1 family)

Skeletal Hands:
syndactyly (1 family)

Neurologic Peripheral Nervous System:
areflexia
distal sensory impairment
gait abnormalities
decreased nerve conduction velocities
sural nerve biopsy shows loss of large myelinated fibers
more
Skeletal Feet:
pes planus (1 family)
syndactyly (1 family)

Head And Neck Head:
microcephaly (1 family)

Genitourinary Bladder:
urinary incontinence (1 family)

Clinical features from OMIM:

615284

Drugs & Therapeutics for Charcot-Marie-Tooth Disease, Type 4b3

Search Clinical Trials , NIH Clinical Center for Charcot-Marie-Tooth Disease, Type 4b3

Genetic Tests for Charcot-Marie-Tooth Disease, Type 4b3

Genetic tests related to Charcot-Marie-Tooth Disease, Type 4b3:

# Genetic test Affiliating Genes
1 Charcot-Marie-Tooth Disease, Type 4b3 30 SBF1

Anatomical Context for Charcot-Marie-Tooth Disease, Type 4b3

MalaCards organs/tissues related to Charcot-Marie-Tooth Disease, Type 4b3:

42
Brain

Publications for Charcot-Marie-Tooth Disease, Type 4b3

Articles related to Charcot-Marie-Tooth Disease, Type 4b3:

# Title Authors Year
1
SET binding factor 1 (SBF1) mutation causes Charcot-Marie-tooth disease type 4B3. ( 24799518 )
2014
2
SET binding factor 1 (SBF1) mutation causes Charcot-Marie-Tooth disease type 4B3. ( 23749797 )
2013
3
A novel syndromic form of sensory-motor polyneuropathy is linked to chromosome 22q13.31-q13.33. ( 21210780 )
2011

Variations for Charcot-Marie-Tooth Disease, Type 4b3

UniProtKB/Swiss-Prot genetic disease variations for Charcot-Marie-Tooth Disease, Type 4b3:

76
# Symbol AA change Variation ID SNP ID
1 SBF1 p.Met418Val VAR_070046 rs587776986
2 SBF1 p.Thr1565Ala VAR_070047 rs200488568

ClinVar genetic disease variations for Charcot-Marie-Tooth Disease, Type 4b3:

6 (show all 12)
# Gene Variation Type Significance SNP ID Assembly Location
1 SBF1 NM_002972.3(SBF1): c.1249A> G (p.Met417Val) single nucleotide variant Pathogenic rs587776986 GRCh37 Chromosome 22, 50903513: 50903513
2 SBF1 NM_002972.3(SBF1): c.1249A> G (p.Met417Val) single nucleotide variant Pathogenic rs587776986 GRCh38 Chromosome 22, 50465084: 50465084
3 SBF1 NM_002972.3(SBF1): c.4768A> G (p.Thr1590Ala) single nucleotide variant Likely pathogenic rs200488568 GRCh37 Chromosome 22, 50893287: 50893287
4 SBF1 NM_002972.3(SBF1): c.4768A> G (p.Thr1590Ala) single nucleotide variant Likely pathogenic rs200488568 GRCh38 Chromosome 22, 50454858: 50454858
5 SBF1 NM_002972.3(SBF1): c.1327G> A (p.Asp443Asn) single nucleotide variant Pathogenic/Likely pathogenic rs690016543 GRCh37 Chromosome 22, 50903435: 50903435
6 SBF1 NM_002972.3(SBF1): c.1327G> A (p.Asp443Asn) single nucleotide variant Pathogenic/Likely pathogenic rs690016543 GRCh38 Chromosome 22, 50465006: 50465006
7 SBF1 NM_002972.3(SBF1): c.2605G> A (p.Val869Met) single nucleotide variant Uncertain significance rs200365973 GRCh37 Chromosome 22, 50900263: 50900263
8 SBF1 NM_002972.3(SBF1): c.2605G> A (p.Val869Met) single nucleotide variant Uncertain significance rs200365973 GRCh38 Chromosome 22, 50461834: 50461834
9 SBF1 NM_002972.3(SBF1): c.4378T> G (p.Leu1460Val) single nucleotide variant Pathogenic rs1404020990 GRCh37 Chromosome 22, 50893829: 50893829
10 SBF1 NM_002972.3(SBF1): c.4378T> G (p.Leu1460Val) single nucleotide variant Pathogenic rs1404020990 GRCh38 Chromosome 22, 50455400: 50455400
11 SBF1 NM_002972.3(SBF1): c.1448C> G (p.Ala483Gly) single nucleotide variant Uncertain significance rs1556430522 GRCh38 Chromosome 22, 50464722: 50464722
12 SBF1 NM_002972.3(SBF1): c.1448C> G (p.Ala483Gly) single nucleotide variant Uncertain significance rs1556430522 GRCh37 Chromosome 22, 50903151: 50903151

Expression for Charcot-Marie-Tooth Disease, Type 4b3

Search GEO for disease gene expression data for Charcot-Marie-Tooth Disease, Type 4b3.

Pathways for Charcot-Marie-Tooth Disease, Type 4b3

Pathways related to Charcot-Marie-Tooth Disease, Type 4b3 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.58 SBF1 SBF2

GO Terms for Charcot-Marie-Tooth Disease, Type 4b3

Cellular components related to Charcot-Marie-Tooth Disease, Type 4b3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 vacuolar membrane GO:0005774 8.62 MTMR2 SBF2

Biological processes related to Charcot-Marie-Tooth Disease, Type 4b3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein dephosphorylation GO:0006470 9.26 MTMR2 SBF1
2 regulation of GTPase activity GO:0043087 9.16 SBF1 SBF2
3 phosphatidylinositol biosynthetic process GO:0006661 8.96 MTMR2 SBF1
4 protein tetramerization GO:0051262 8.32 SBF2

Molecular functions related to Charcot-Marie-Tooth Disease, Type 4b3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Rab guanyl-nucleotide exchange factor activity GO:0017112 9.16 SBF1 SBF2
2 protein tyrosine/serine/threonine phosphatase activity GO:0008138 8.96 MTMR2 SBF1
3 phosphatase regulator activity GO:0019208 8.62 SBF1 SBF2

Sources for Charcot-Marie-Tooth Disease, Type 4b3

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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