CMT4B2
MCID: CHR519
MIFTS: 41

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

Categories: Eye diseases, Genetic diseases, Metabolic diseases, Muscle diseases, Nephrological 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 57 29 13 6 40 72
Charcot-Marie-Tooth Disease Type 4b2 12 53 59 15
Cmt4b2 57 12 59 74
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 74
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 74
Charcot-Marie-Tooth Disease Demyelinating Autosomal Recessive 4b2 74
Charcot Marie Tooth Disease Type 4b2 53
Charcot-Marie-Tooth Disease 4b2 74
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 autosomal recessive inheritance heterogeneous
Onset and clinical course juvenile onset


Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0110190
MeSH 44 D002607
ICD10 33 G60.0
MESH via Orphanet 45 C535421
ICD10 via Orphanet 34 G60.0
UMLS via Orphanet 73 C1858278
Orphanet 59 ORPHA99956
UMLS 72 C1858278

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

UniProtKB/Swiss-Prot : 74 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 early-onset glaucoma and sensory peripheral neuropathy. 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 areflexia

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 D
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, Dominant Intermediate E
Charcot-Marie-Tooth Disease, Dominant Intermediate F Charcot-Marie-Tooth Disease, Type 4b3
Charcot-Marie-Tooth Disease, Recessive Intermediate C Charcot-Marie-Tooth Disease, Recessive Intermediate D
Charcot-Marie-Tooth Disease, Type 4k Charcot-Marie-Tooth Disease, Dominant Intermediate G
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 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 21)
# Related Disease Score Top Affiliating Genes
1 early-onset glaucoma 29.7 SBF2 SBF1 MTMR2 MTM1
2 sensory peripheral neuropathy 29.3 PRX MTMR2 GDAP1
3 neuropathy 29.0 TDP1 SBF2 PRX GDAP1
4 peripheral nervous system disease 28.9 PRX MTMR2 MTM1 GDAP1
5 tooth disease 28.7 SBF2 SBF1 PRX MTMR2 GDAP1
6 charcot-marie-tooth disease 28.1 SBF2 SBF1 PRX MTMR2 MTM1 GDAP1
7 charcot-marie-tooth disease, type 4b1 27.8 SBF2 SBF1 PRX MTMR2 MTM1 GDAP1
8 neuropathy, congenital hypomyelinating, 1, autosomal recessive 11.4
9 autosomal recessive disease 10.2
10 charcot-marie-tooth disease, type 4j 10.0 SBF2 MTMR2
11 axonal neuropathy 9.9 TDP1 GDAP1
12 charcot-marie-tooth disease, demyelinating, type 1a 9.7 MTMR2 GDAP1
13 neuropathy, hereditary, with liability to pressure palsies 9.6 MTMR2 GDAP1
14 centronuclear myopathy 9.6 SBF1 MTMR2 MTM1
15 charcot-marie-tooth disease and deafness 9.4 MTMR2 GDAP1
16 charcot-marie-tooth disease, axonal, type 2e 9.2 SBF2 MTMR2 MTM1 GDAP1
17 hypertrophic neuropathy of dejerine-sottas 9.1 PRX MTMR2 GDAP1
18 spinocerebellar ataxia type 1 with axonal neuropathy 8.9 TDP1 SBF2 PRX MTMR2
19 charcot-marie-tooth disease, type 4b3 8.8 SBF2 SBF1 MTMR2 MTM1 GDAP1
20 charcot-marie-tooth disease, demyelinating, type 4f 8.4 TDP1 SBF2 PRX MTMR2 GDAP1
21 charcot-marie-tooth disease, type 4a 8.4 TDP1 SBF2 PRX MTMR2 GDAP1

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:

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

Symptoms via clinical synopsis from OMIM:

57
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 Hands:
claw hand deformities (in severe cases)

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

Skeletal Feet:
pes cavus
foot deformities
hammertoes
talipes equinus

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:

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
Brain, Spinal Cord

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

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

(show all 26)
# Title Authors PMID Year
1
A new SBF2 mutation in a family with recessive demyelinating Charcot-Marie-Tooth (CMT4B2). 38 8 71
15477569 2004
2
Mutations in MTMR13, a new pseudophosphatase homologue of MTMR2 and Sbf1, in two families with an autosomal recessive demyelinating form of Charcot-Marie-Tooth disease associated with early-onset glaucoma. 38 8 71
12687498 2003
3
Mutation of the SBF2 gene, encoding a novel member of the myotubularin family, in Charcot-Marie-Tooth neuropathy type 4B2/11p15. 38 8 71
12554688 2003
4
SET binding factor 2 (SBF2) mutation causes CMT4B with juvenile onset glaucoma. 8 71
15304601 2004
5
Hereditary motor and sensory neuropathy with myelin folding and juvenile onset glaucoma. 8 71
10932274 2000
6
Genetic heterogeneity in autosomal recessive hereditary motor and sensory neuropathy with focally folded myelin sheaths (CMT4B). 8 71
9521281 1998
7
Loss of the inactive myotubularin-related phosphatase Mtmr13 leads to a Charcot-Marie-Tooth 4B2-like peripheral neuropathy in mice. 38 8
18349142 2008
8
Mtmr13/Sbf2-deficient mice: an animal model for CMT4B2. 38 8
17855448 2007
9
Charcot-Marie-Tooth Neuropathy Type 4 38 71
20301641 1998
10
Charcot-Marie-Tooth (CMT) Hereditary Neuropathy Overview 71
20301532 1998
11
A multicenter retrospective study of charcot-marie-tooth disease type 4B (CMT4B) associated with mutations in myotubularin-related proteins (MTMRs). 38
31070812 2019
12
Novel SBF2 mutations and clinical spectrum of Charcot-Marie-Tooth neuropathy type 4B2. 38
30028002 2018
13
An In Vitro Model of Charcot-Marie-Tooth Disease Type 4B2 Provides Insight Into the Roles of MTMR13 and MTMR2 in Schwann Cell Myelination. 38
30419760 2018
14
"Fork and bracket" syndrome expands the spectrum of SBF1-related sensory motor polyneuropathies. 38
27123480 2016
15
Sural nerve biopsy and functional studies support the pathogenic role of a novel MPZ mutation. 38
25388615 2015
16
Charcot-Marie-Tooth 4B2 caused by a novel mutation in the MTMR13/SBF2 gene in two related Portuguese families. 38
25873783 2014
17
Identification of a novel SBF2 frameshift mutation in charcot-marie-tooth disease type 4B2 using whole-exome sequencing. 38
25462154 2014
18
SET binding factor 1 (SBF1) mutation causes Charcot-Marie-Tooth disease type 4B3. 38
23749797 2013
19
The CMT4B disease-causing phosphatases Mtmr2 and Mtmr13 localize to the Schwann cell cytoplasm and endomembrane compartments, where they depend upon each other to achieve wild-type levels of protein expression. 38
23297362 2013
20
Genetic study of demyelinating form of autosomal-recessive Charcot-Marie-tooth diseases in a Turkish family. 38
19922348 2009
21
[Hereditary neuropathy: recent advance]. 38
19198150 2008
22
Charcot-Marie-Tooth type 4B demyelinating neuropathy: deciphering the role of MTMR phosphatases. 38
17880751 2007
23
[Molecular genetics of inherited neuropathies]. 38
17432174 2006
24
Cloning, expression and characterization of the murine orthologue of SBF2, the gene mutated in Charcot-Marie-Tooth disease type 4B2. 38
16750429 2006
25
[Molecular genetics of inherited neuropathies]. 38
16541790 2006
26
The phosphoinositide-3-phosphatase MTMR2 associates with MTMR13, a membrane-associated pseudophosphatase also mutated in type 4B Charcot-Marie-Tooth disease. 38
15998640 2005

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 GRCh37 Pos GRCh38 Pos
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.5014_5016del (p.Lys1672del) deletion Uncertain significance rs750958357 11:9809202-9809204 11:9787655-9787657
4 SBF2 NM_030962.3(SBF2): c.1967G> C (p.Cys656Ser) single nucleotide variant Uncertain significance rs138120231 11:9879906-9879906 11:9858359-9858359
5 SBF2 NM_030962.3(SBF2): c.3935G> A (p.Arg1312Gln) single nucleotide variant Uncertain significance 11:9838430-9838430 11:9816883-9816883
6 SBF2 NM_030962.3(SBF2): c.5041C> T (p.Gln1681Ter) single nucleotide variant Uncertain significance 11:9806862-9806862 11:9785315-9785315
7 SBF2 NM_030962.3(SBF2): c.1024C> T (p.Arg342Ter) single nucleotide variant Uncertain significance 11:10015497-10015497 11:9993950-9993950
8 SBF2 NM_030962.3(SBF2): c.3292C> G (p.Leu1098Val) single nucleotide variant Benign/Likely benign rs117957652 11:9861208-9861208 11:9839661-9839661
9 SBF2 NM_030962.3(SBF2): c.4571-6C> T single nucleotide variant Benign rs2645029 11:9812236-9812236 11:9790689-9790689
10 SBF2 NM_030962.3(SBF2): c.753-16T> A single nucleotide variant Benign rs7128234 11:10022585-10022585 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 SBF2 SBF1

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 TDP1 SBF2 SBF1 PRX MTMR2 MTM1
2 vacuolar membrane GO:0005774 8.62 SBF2 MTMR2

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 MTMR2 MTM1
2 protein dephosphorylation GO:0006470 9.33 SBF1 MTMR2 MTM1
3 regulation of GTPase activity GO:0043087 9.32 SBF2 SBF1
4 protein tetramerization GO:0051262 8.96 SBF2
5 phosphatidylinositol dephosphorylation GO:0046856 8.96 MTMR2 MTM1
6 phosphatidylinositol biosynthetic process GO:0006661 8.8 SBF1 MTMR2 MTM1

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 MTMR2 MTM1
2 protein tyrosine phosphatase activity GO:0004725 9.4 MTMR2 MTM1
3 phosphatidylinositol binding GO:0035091 9.37 SBF2 MTM1
4 Rab guanyl-nucleotide exchange factor activity GO:0017112 9.32 SBF2 SBF1
5 protein tyrosine/serine/threonine phosphatase activity GO:0008138 9.26 SBF1 MTMR2
6 phosphatidylinositol-3-phosphatase activity GO:0004438 9.16 MTMR2 MTM1
7 phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity GO:0052629 8.96 MTMR2 MTM1
8 phosphatase regulator activity GO:0019208 8.62 SBF2 SBF1

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

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 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 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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