CMT4B3
MCID: CHR504
MIFTS: 39

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 57 29 6 40 73
Cmt4b3 57 12 59 75
Charcot-Marie-Tooth Disease Type 4b3 12 59 15
Charcot-Marie-Tooth Disease with Focally Folded Myelin 59
Charcot-Marie-Tooth Neuropathy Type 4b3 75
Charcot-Marie-Tooth Disease 4b3 75

Characteristics:

Orphanet epidemiological data:

59
charcot-marie-tooth disease type 4b3
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

57
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:

32
charcot-marie-tooth disease, type 4b3:
Onset and clinical course progressive
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Rare neurological diseases


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

UniProtKB/Swiss-Prot : 75 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 are PI Metabolism and 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 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 2dd 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 32.4 GDAP1 MTMR2
2 charcot-marie-tooth disease, type 4b2 31.9 GDAP1 MTM1 MTMR2 SBF1 SBF2
3 charcot-marie-tooth disease, type 4b1 31.6 GDAP1 MTM1 MTMR2 SBF1 SBF2
4 tooth disease 30.2 GDAP1 MTMR2 SBF1 SBF2
5 charcot-marie-tooth disease 29.9 GDAP1 MTM1 MTMR2 SBF1 SBF2
6 charcot-marie-tooth disease, demyelinating, type 1b 11.7
7 spinocerebellar ataxia type 1 with axonal neuropathy 9.9 MTMR2 SBF2
8 charcot-marie-tooth disease, type 4j 9.9 MTMR2 SBF2
9 neuropathy, hereditary, with liability to pressure palsies 9.8 GDAP1 MTMR2
10 centronuclear myopathy 9.8 MTM1 MTMR2 SBF1
11 charcot-marie-tooth disease and deafness 9.8 GDAP1 MTMR2
12 hypertrophic neuropathy of dejerine-sottas 9.8 GDAP1 MTMR2
13 sensory peripheral neuropathy 9.7 GDAP1 MTMR2
14 peripheral nervous system disease 9.7 GDAP1 MTM1 MTMR2
15 charcot-marie-tooth disease, demyelinating, type 4f 9.7 GDAP1 MTMR2 SBF2
16 charcot-marie-tooth disease, type 4a 9.6 GDAP1 MTMR2 SBF2
17 early-onset glaucoma 9.6 MTM1 MTMR2 SBF1 SBF2
18 charcot-marie-tooth disease, axonal, type 2e 9.5 GDAP1 MTM1 MTMR2 SBF2
19 neuropathy, congenital hypomyelinating or amyelinating, autosomal recessive 9.3 GDAP1 MTM1 MTMR2 SBF1 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

Symptoms via clinical synopsis from OMIM:

57
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

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

32 (show all 15)
# Description HPO Frequency HPO Source Accession
1 brain atrophy 32 occasional (7.5%) HP:0012444
2 intellectual disability 32 occasional (7.5%) HP:0001249
3 gait disturbance 32 HP:0001288
4 scoliosis 32 HP:0002650
5 pes planus 32 HP:0001763
6 microcephaly 32 HP:0000252
7 strabismus 32 occasional (7.5%) HP:0000486
8 decreased nerve conduction velocity 32 HP:0000762
9 areflexia 32 HP:0001284
10 ophthalmoplegia 32 occasional (7.5%) HP:0000602
11 limb muscle weakness 32 HP:0003690
12 urinary incontinence 32 occasional (7.5%) HP:0000020
13 distal sensory impairment 32 HP:0002936
14 syndactyly 32 occasional (7.5%) HP:0001159
15 onion bulb formation 32 HP:0003383

MGI Mouse Phenotypes related to Charcot-Marie-Tooth Disease, Type 4b3:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 reproductive system MP:0005389 8.92 MTM1 MTMR2 SBF1 SBF2

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 29 SBF1

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

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

41
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

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

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

75
# 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
# 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 Pathogenic rs200488568 GRCh37 Chromosome 22, 50893287: 50893287
4 SBF1 NM_002972.3(SBF1): c.4768A> G (p.Thr1590Ala) single nucleotide variant 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.4378T> G (p.Leu1460Val) single nucleotide variant Pathogenic GRCh37 Chromosome 22, 50893829: 50893829
8 SBF1 NM_002972.3(SBF1): c.4378T> G (p.Leu1460Val) single nucleotide variant Pathogenic GRCh38 Chromosome 22, 50455400: 50455400
9 SBF1 NM_002972.3(SBF1): c.1448C> G (p.Ala483Gly) single nucleotide variant Uncertain significance GRCh38 Chromosome 22, 50464722: 50464722
10 SBF1 NM_002972.3(SBF1): c.1448C> G (p.Ala483Gly) single nucleotide variant Uncertain significance 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

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 cytosol GO:0005829 9.35 GDAP1 MTM1 MTMR2 SBF1 SBF2
2 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 dephosphorylation GO:0016311 9.4 MTM1 MTMR2
2 peptidyl-tyrosine dephosphorylation GO:0035335 9.37 MTM1 MTMR2
3 regulation of GTPase activity GO:0043087 9.32 SBF1 SBF2
4 protein tetramerization GO:0051262 9.26 MTMR2 SBF2
5 phosphatidylinositol dephosphorylation GO:0046856 9.16 MTM1 MTMR2
6 protein dephosphorylation GO:0006470 9.13 MTM1 MTMR2 SBF1
7 phosphatidylinositol biosynthetic process GO:0006661 8.8 MTM1 MTMR2 SBF1

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

# Name GO ID Score Top Affiliating Genes
1 phosphatase activity GO:0016791 9.43 MTM1 MTMR2
2 protein tyrosine phosphatase activity GO:0004725 9.4 MTM1 MTMR2
3 phosphatidylinositol binding GO:0035091 9.37 MTM1 SBF2
4 Rab guanyl-nucleotide exchange factor activity GO:0017112 9.32 SBF1 SBF2
5 protein tyrosine/serine/threonine phosphatase activity GO:0008138 9.26 MTMR2 SBF1
6 phosphatidylinositol-3-phosphatase activity GO:0004438 9.16 MTM1 MTMR2
7 phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity GO:0052629 8.96 MTM1 MTMR2
8 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 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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