MCID: CHR519
MIFTS: 40

Charcot-Marie-Tooth Disease, Type 4b2

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

Aliases & Classifications for Charcot-Marie-Tooth Disease, Type 4b2

MalaCards integrated aliases for Charcot-Marie-Tooth Disease, Type 4b2:

Name: Charcot-Marie-Tooth Disease, Type 4b2 57 29 13 6 40 73
Charcot-Marie-Tooth Disease Type 4b2 12 53 59 15
Cmt4b2 57 12 59 75
Charcot-Marie-Tooth Disease, with Focally Folded Myelin Sheaths, Autosomal Recessive, Type 4b2 57 53
Charcot-Marie-Tooth Neuropathy, Type 4b2 57 53
Charcot-Marie-Tooth Neuropathy Type 4b2 12 75
Autosomal Recessive Charcot-Marie-Tooth Disease with Focally Folded Myelin Sheaths Type 4b2 12
Charcot-Marie-Tooth Disease Autosomal Recessive with Focally Folded Myelin Sheaths 4b2 75
Charcot-Marie-Tooth Disease Demyelinating Autosomal Recessive 4b2 75
Charcot Marie Tooth Disease Type 4b2 53
Charcot-Marie-Tooth Disease 4b2 75
Cmt 4b2 53

Characteristics:

Orphanet epidemiological data:

59
charcot-marie-tooth disease type 4b2
Inheritance: Autosomal recessive; Age of onset: Childhood;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
upper limb involvement usually occurs later
onset in first or second decade (range 4 to 13 years)
onset in feet and legs (peroneal distribution)
patients with glaucoma have nonsense or truncating sbf2 mutations
genetic heterogeneity (see cmt4b1, )


HPO:

32
charcot-marie-tooth disease, type 4b2:
Inheritance heterogeneous autosomal recessive inheritance
Onset and clinical course juvenile onset


Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

OMIM 57 604563
Disease Ontology 12 DOID:0110190
ICD10 33 G60.0
Orphanet 59 ORPHA99956
MESH via Orphanet 45 C535421
ICD10 via Orphanet 34 G60.0
UMLS via Orphanet 74 C1858278
MeSH 44 D002607
UMLS 73 C1858278

Summaries for Charcot-Marie-Tooth Disease, Type 4b2

UniProtKB/Swiss-Prot : 75 Charcot-Marie-Tooth disease 4B2: 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 4b2, also known as charcot-marie-tooth disease type 4b2, is related to neuropathy, congenital hypomyelinating or amyelinating, autosomal recessive and tooth disease. An important gene associated with Charcot-Marie-Tooth Disease, Type 4b2 is SBF2 (SET Binding Factor 2), and among its related pathways/superpathways is RAB GEFs exchange GTP for GDP on RABs. Affiliated tissues include spinal cord, brain and eye, and related phenotypes are sensorineural hearing impairment and glaucoma

Disease Ontology : 12 A Charcot-Marie-Tooth disease type 4 that has material basis in mutation in the SBF2 gene.

NIH Rare Diseases : 53 Charcot-Marie-Tooth disease type 4B2 (CMT4B2) is a disorder that affects the peripheral nerves. Peripheral nerves connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound. Damage to the peripheral nerves can result in loss of sensation and wasting (atrophy) of muscles in the feet, legs, and hands. CMT4B2 can also cause glaucoma (damage to the eye’s optic nerve). There is currently no cure for CMT4B2, but physical therapy, occupational therapy, braces and other orthopedic devices, pain medication, and orthopedic surgery can help manage and improve symptoms. CMT4B2 is inherited in an autosomal recessive fashion. It is caused by mutations in the SBF1 gene.

OMIM : 57 Autosomal recessive Charcot-Marie-Tooth disease type 4B is a demyelinating hereditary motor and sensory neuropathy characterized by abnormal folding of myelin sheaths. CMT4B1 (601382) is a clinically similar disorder caused by mutation in the MTMR2 gene (603557) on 11q22. For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive demyelinating CMT, see CMT4A (214400). (604563)

Related Diseases for Charcot-Marie-Tooth Disease, Type 4b2

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 4b2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 19)
# Related Disease Score Top Affiliating Genes
1 neuropathy, congenital hypomyelinating or amyelinating, autosomal recessive 27.9 GDAP1 MTM1 MTMR2 PRX SBF1 SBF2
2 tooth disease 27.7 GDAP1 MTMR2 PRX SBF1 SBF2
3 charcot-marie-tooth disease 26.9 GDAP1 MTM1 MTMR2 PRX SBF1 SBF2
4 charcot-marie-tooth disease, type 4j 10.1 MTMR2 SBF2
5 charcot-marie-tooth disease, demyelinating, type 1a 9.8 GDAP1 MTMR2
6 charcot-marie-tooth disease and deafness 9.7 GDAP1 MTMR2
7 peripheral nervous system disease 9.5 GDAP1 MTMR2
8 hereditary neuropathies 9.5 MTMR2 PRX
9 axonal neuropathy 9.2 GDAP1 TDP1
10 early-onset glaucoma 9.2 MTM1 MTMR2 SBF1 SBF2
11 centronuclear myopathy 9.2 MTM1 MTMR2 SBF1 SBF2
12 charcot-marie-tooth disease, axonal, type 2e 9.0 GDAP1 MTM1 MTMR2 SBF2
13 hypertrophic neuropathy of dejerine-sottas 8.9 GDAP1 MTMR2 PRX
14 sensory peripheral neuropathy 8.9 GDAP1 MTMR2 PRX
15 charcot-marie-tooth disease, type 4b3 8.5 GDAP1 MTM1 MTMR2 SBF1 SBF2
16 neuropathy 8.4 GDAP1 PRX SBF2 TDP1
17 charcot-marie-tooth disease, demyelinating, type 4f 8.0 GDAP1 MTMR2 PRX SBF2 TDP1
18 charcot-marie-tooth disease, type 4a 8.0 GDAP1 MTMR2 PRX SBF2 TDP1
19 charcot-marie-tooth disease, type 4b1 7.5 GDAP1 MTM1 MTMR2 PRX SBF1 SBF2

Graphical network of the top 20 diseases related to Charcot-Marie-Tooth Disease, Type 4b2:



Diseases related to Charcot-Marie-Tooth Disease, Type 4b2

Symptoms & Phenotypes for Charcot-Marie-Tooth Disease, Type 4b2

Symptoms via clinical synopsis from OMIM:

57
Skeletal Feet:
pes cavus
foot deformities
hammertoes
talipes equinus

Skeletal Hands:
claw hand deformities (in severe cases)

Head And Neck Ears:
sensorineural hearing loss (described in 1 family)

Neurologic Peripheral Nervous System:
areflexia
difficulty walking
hyporeflexia
distal limb muscle weakness due to peripheral neuropathy
distal limb muscle atrophy due to peripheral neuropathy
more
Skeletal Spine:
kyphoscoliosis may be present

Head And Neck Eyes:
glaucoma, open-angle, early-onset (occurs in patients with nonsense or truncating mutations in the sbf2 gene)
glaucoma may precede development of neuropathy


Clinical features from OMIM:

604563

Human phenotypes related to Charcot-Marie-Tooth Disease, Type 4b2:

32 (show all 20)
# Description HPO Frequency HPO Source Accession
1 sensorineural hearing impairment 32 HP:0000407
2 glaucoma 32 HP:0000501
3 split hand 32 HP:0001171
4 ulnar claw 32 HP:0001178
5 hyporeflexia 32 HP:0001265
6 areflexia 32 HP:0001284
7 pes cavus 32 HP:0001761
8 talipes equinovarus 32 HP:0001762
9 hammertoe 32 HP:0001765
10 difficulty walking 32 HP:0002355
11 distal muscle weakness 32 HP:0002460
12 kyphoscoliosis 32 HP:0002751
13 distal sensory impairment 32 HP:0002936
14 steppage gait 32 HP:0003376
15 decreased number of peripheral myelinated nerve fibers 32 HP:0003380
16 onion bulb formation 32 HP:0003383
17 decreased motor nerve conduction velocity 32 HP:0003431
18 segmental peripheral demyelination/remyelination 32 HP:0003481
19 distal amyotrophy 32 HP:0003693
20 foot dorsiflexor weakness 32 HP:0009027

MGI Mouse Phenotypes related to Charcot-Marie-Tooth Disease, Type 4b2:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.1 GDAP1 MTM1 MTMR2 PRX SBF2 TDP1

Drugs & Therapeutics for Charcot-Marie-Tooth Disease, Type 4b2

Search Clinical Trials , NIH Clinical Center for Charcot-Marie-Tooth Disease, Type 4b2

Genetic Tests for Charcot-Marie-Tooth Disease, Type 4b2

Genetic tests related to Charcot-Marie-Tooth Disease, Type 4b2:

# Genetic test Affiliating Genes
1 Charcot-Marie-Tooth Disease, Type 4b2 29 SBF2

Anatomical Context for Charcot-Marie-Tooth Disease, Type 4b2

MalaCards organs/tissues related to Charcot-Marie-Tooth Disease, Type 4b2:

41
Spinal Cord, Brain, Eye

Publications for Charcot-Marie-Tooth Disease, Type 4b2

Articles related to Charcot-Marie-Tooth Disease, Type 4b2:

# Title Authors Year
1
Identification of a novel SBF2 frameshift mutation in charcot-marie-tooth disease type 4B2 using whole-exome sequencing. ( 25462154 )
2014
2
Cloning, expression and characterization of the murine orthologue of SBF2, the gene mutated in Charcot-Marie-Tooth disease type 4B2. ( 16750429 )
2006

Variations for Charcot-Marie-Tooth Disease, Type 4b2

ClinVar genetic disease variations for Charcot-Marie-Tooth Disease, Type 4b2:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 SBF2 SBF2, EX11-12DEL deletion Pathogenic
2 SBF2 SBF2, IVS32DS, G-C, +1 single nucleotide variant Pathogenic
3 SBF2 NM_030962.3(SBF2): c.4571-6C> T single nucleotide variant Benign rs2645029 GRCh38 Chromosome 11, 9790689: 9790689
4 SBF2 NM_030962.3(SBF2): c.4571-6C> T single nucleotide variant Benign rs2645029 GRCh37 Chromosome 11, 9812236: 9812236
5 SBF2 NM_030962.3(SBF2): c.5451+2T> G single nucleotide variant Likely pathogenic rs886042830 GRCh37 Chromosome 11, 9803052: 9803052
6 SBF2 NM_030962.3(SBF2): c.5451+2T> G single nucleotide variant Likely pathogenic rs886042830 GRCh38 Chromosome 11, 9781505: 9781505
7 SBF2 NM_030962.3(SBF2): c.5014_5016delAAA (p.Lys1672del) deletion Uncertain significance rs750958357 GRCh38 Chromosome 11, 9787655: 9787657
8 SBF2 NM_030962.3(SBF2): c.5014_5016delAAA (p.Lys1672del) deletion Uncertain significance rs750958357 GRCh37 Chromosome 11, 9809202: 9809204
9 SBF2 NM_030962.3(SBF2): c.753-16T> A single nucleotide variant Benign rs7128234 GRCh37 Chromosome 11, 10022585: 10022585
10 SBF2 NM_030962.3(SBF2): c.753-16T> A single nucleotide variant Benign rs7128234 GRCh38 Chromosome 11, 10001038: 10001038

Expression for Charcot-Marie-Tooth Disease, Type 4b2

Search GEO for disease gene expression data for Charcot-Marie-Tooth Disease, Type 4b2.

Pathways for Charcot-Marie-Tooth Disease, Type 4b2

Pathways related to Charcot-Marie-Tooth Disease, Type 4b2 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 4b2

Cellular components related to Charcot-Marie-Tooth Disease, Type 4b2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 9.5 GDAP1 MTM1 MTMR2 PRX SBF1 SBF2
2 vacuolar membrane GO:0005774 8.62 MTMR2 SBF2

Biological processes related to Charcot-Marie-Tooth Disease, Type 4b2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 peptidyl-tyrosine dephosphorylation GO:0035335 9.37 MTM1 MTMR2
2 regulation of GTPase activity GO:0043087 9.32 SBF1 SBF2
3 protein tetramerization GO:0051262 9.26 MTMR2 SBF2
4 phosphatidylinositol dephosphorylation GO:0046856 9.16 MTM1 MTMR2
5 protein dephosphorylation GO:0006470 9.13 MTM1 MTMR2 SBF1
6 phosphatidylinositol biosynthetic process GO:0006661 8.8 MTM1 MTMR2 SBF1

Molecular functions related to Charcot-Marie-Tooth Disease, Type 4b2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 phosphatase activity GO:0016791 9.43 MTM1 MTMR2
2 phosphatidylinositol binding GO:0035091 9.4 MTM1 SBF2
3 protein tyrosine phosphatase activity GO:0004725 9.37 MTM1 MTMR2
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 4b2

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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