CMT4B2
MCID: CHR519
MIFTS: 40

Charcot-Marie-Tooth Disease, Type 4b2 (CMT4B2)

Categories: Eye diseases, Genetic diseases, Metabolic diseases, Muscle diseases, Neuronal diseases, Rare 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 58 30 13 6 41 74
Charcot-Marie-Tooth Disease Type 4b2 12 54 60 15
Cmt4b2 58 12 60 76
Charcot-Marie-Tooth Disease, with Focally Folded Myelin Sheaths, Autosomal Recessive, Type 4b2 58 54
Charcot-Marie-Tooth Neuropathy, Type 4b2 58 54
Charcot-Marie-Tooth Neuropathy Type 4b2 12 76
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 76
Charcot-Marie-Tooth Disease Demyelinating Autosomal Recessive 4b2 76
Charcot Marie Tooth Disease Type 4b2 54
Charcot-Marie-Tooth Disease 4b2 76
Cmt 4b2 54

Characteristics:

Orphanet epidemiological data:

60
charcot-marie-tooth disease type 4b2
Inheritance: Autosomal recessive; Age of onset: Childhood;

OMIM:

58
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:

33
charcot-marie-tooth disease, type 4b2:
Inheritance heterogeneous autosomal recessive inheritance
Onset and clinical course juvenile onset


Classifications:

Orphanet: 60  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0110190
OMIM 58 604563
MeSH 45 D002607
ICD10 34 G60.0
MESH via Orphanet 46 C535421
ICD10 via Orphanet 35 G60.0
UMLS via Orphanet 75 C1858278
Orphanet 60 ORPHA99956
UMLS 74 C1858278

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

UniProtKB/Swiss-Prot : 76 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 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 brain and spinal cord, and related phenotypes are sensorineural hearing impairment and pes cavus

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

NIH Rare Diseases : 54 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 : 58 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 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 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 20)
# Related Disease Score Top Affiliating Genes
1 neuropathy 29.7 GDAP1 PRX SBF2 TDP1
2 tooth disease 29.6 GDAP1 MTMR2 PRX SBF1 SBF2
3 charcot-marie-tooth disease 29.3 GDAP1 MTM1 MTMR2 PRX SBF1 SBF2
4 neuropathy, congenital hypomyelinating, 1, autosomal recessive 11.3
5 charcot-marie-tooth disease, type 4j 10.0 MTMR2 SBF2
6 axonal neuropathy 9.9 GDAP1 TDP1
7 charcot-marie-tooth disease, demyelinating, type 1a 9.8 GDAP1 MTMR2
8 neuropathy, hereditary, with liability to pressure palsies 9.8 GDAP1 MTMR2
9 centronuclear myopathy 9.7 MTM1 MTMR2 SBF1
10 charcot-marie-tooth disease and deafness 9.7 GDAP1 MTMR2
11 early-onset glaucoma 9.6 MTM1 MTMR2 SBF1 SBF2
12 charcot-marie-tooth disease, axonal, type 2e 9.5 GDAP1 MTM1 MTMR2 SBF2
13 hypertrophic neuropathy of dejerine-sottas 9.4 GDAP1 MTMR2 PRX
14 sensory peripheral neuropathy 9.4 GDAP1 MTMR2 PRX
15 spinocerebellar ataxia type 1 with axonal neuropathy 9.3 MTMR2 PRX SBF2 TDP1
16 charcot-marie-tooth disease, type 4b3 9.2 GDAP1 MTM1 MTMR2 SBF1 SBF2
17 peripheral nervous system disease 9.2 GDAP1 MTM1 MTMR2 PRX
18 charcot-marie-tooth disease, demyelinating, type 4f 9.0 GDAP1 MTMR2 PRX SBF2 TDP1
19 charcot-marie-tooth disease, type 4a 9.0 GDAP1 MTMR2 PRX SBF2 TDP1
20 charcot-marie-tooth disease, type 4b1 8.8 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

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

33 (show all 20)
# Description HPO Frequency HPO Source Accession
1 sensorineural hearing impairment 33 HP:0000407
2 pes cavus 33 HP:0001761
3 decreased motor nerve conduction velocity 33 HP:0003431
4 talipes equinovarus 33 HP:0001762
5 kyphoscoliosis 33 HP:0002751
6 glaucoma 33 HP:0000501
7 areflexia 33 HP:0001284
8 split hand 33 HP:0001171
9 difficulty walking 33 HP:0002355
10 hyporeflexia 33 HP:0001265
11 foot dorsiflexor weakness 33 HP:0009027
12 hammertoe 33 HP:0001765
13 distal muscle weakness 33 HP:0002460
14 steppage gait 33 HP:0003376
15 distal amyotrophy 33 HP:0003693
16 segmental peripheral demyelination/remyelination 33 HP:0003481
17 distal sensory impairment 33 HP:0002936
18 decreased number of peripheral myelinated nerve fibers 33 HP:0003380
19 onion bulb formation 33 HP:0003383
20 ulnar claw 33 HP:0001178

Symptoms via clinical synopsis from OMIM:

58
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

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

47
# 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 30 SBF2

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

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

42
Brain, Spinal Cord

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

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

# Title Authors Year
1
An In Vitro Model of Charcot-Marie-Tooth Disease Type 4B2 Provides Insight Into the Roles of MTMR13 and MTMR2 in Schwann Cell Myelination. ( 30419760 )
2018
2
Identification of a novel SBF2 frameshift mutation in charcot-marie-tooth disease type 4B2 using whole-exome sequencing. ( 25462154 )
2014
3
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 (show all 12)
# 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.3292C> G (p.Leu1098Val) single nucleotide variant Benign/Likely benign rs117957652 GRCh38 Chromosome 11, 9839661: 9839661
4 SBF2 NM_030962.3(SBF2): c.3292C> G (p.Leu1098Val) single nucleotide variant Benign/Likely benign rs117957652 GRCh37 Chromosome 11, 9861208: 9861208
5 SBF2 NM_030962.3(SBF2): c.4571-6C> T single nucleotide variant Benign rs2645029 GRCh38 Chromosome 11, 9790689: 9790689
6 SBF2 NM_030962.3(SBF2): c.4571-6C> T single nucleotide variant Benign rs2645029 GRCh37 Chromosome 11, 9812236: 9812236
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
11 SBF2 NM_030962.3(SBF2): c.3935G> A (p.Arg1312Gln) single nucleotide variant Uncertain significance GRCh37 Chromosome 11, 9838430: 9838430
12 SBF2 NM_030962.3(SBF2): c.3935G> A (p.Arg1312Gln) single nucleotide variant Uncertain significance GRCh38 Chromosome 11, 9816883: 9816883

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 protein dephosphorylation GO:0006470 9.33 MTM1 MTMR2 SBF1
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 8.96 MTM1 MTMR2
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 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 4b2

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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