CMT4J
MCID: CHR420
MIFTS: 39

Charcot-Marie-Tooth Disease, Type 4j (CMT4J)

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

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

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

Name: Charcot-Marie-Tooth Disease, Type 4j 58 54 30 13 6 41 74
Cmt4j 58 12 54 60 76
Charcot-Marie-Tooth Disease Type 4j 12 54 60 15
Charcot-Marie-Tooth Disease, Autosomal Recessive, Type 4j 58 54
Autosomal Recessive Charcot-Marie-Tooth Disease Type 4j 12
Charcot-Marie-Tooth Disease 4j 76

Characteristics:

Orphanet epidemiological data:

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

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
progressive disorder
onset usually in early childhood
some patients may become wheelchair-bound
adult onset may occur
motor impairment more significant than sensory impairment
trauma may accelerate symptoms


HPO:

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


Classifications:

Orphanet: 60  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0110184
OMIM 58 611228
MeSH 45 D002607
ICD10 34 G60.0
ICD10 via Orphanet 35 G60.0
UMLS via Orphanet 75 C1970011
Orphanet 60 ORPHA139515
MedGen 43 C1970011
UMLS 74 C1970011

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

UniProtKB/Swiss-Prot : 76 Charcot-Marie-Tooth disease 4J: 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 4j, also known as cmt4j, is related to charcot-marie-tooth disease and tooth disease. An important gene associated with Charcot-Marie-Tooth Disease, Type 4j is FIG4 (FIG4 Phosphoinositide 5-Phosphatase), and among its related pathways/superpathways are Metabolism and Glycerophospholipid biosynthesis. Related phenotypes are motor delay and gait disturbance

Disease Ontology : 12 A Charcot-Marie-Tooth disease type 4 that has material basis in compound heterozygous mutations in the FIG4 gene on chromosome 6q21.

OMIM : 58 Charcot-Marie-Tooth disease type 4J is an autosomal recessive progressive neurologic disorder with a highly variable phenotype and onset ranging from early childhood to adulthood. Most patients have both proximal and distal asymmetric muscle weakness of the upper and lower limbs. There is significant motor dysfunction, followed by variably progressive sensory loss, which may be mild. Nerve conduction studies and nerve biopsies indicate demyelination as well as axonal loss (summary by Nicholson et al., 2011). For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive demyelinating Charcot-Marie-Tooth disease, see CMT4A (214400). (611228)

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

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

(show all 19)
# Related Disease Score Top Affiliating Genes
1 charcot-marie-tooth disease 30.3 FIG4 MTMR2 SBF2
2 tooth disease 30.3 FIG4 MTMR2 SBF2
3 charcot-marie-tooth neuropathy type 4j 12.1
4 neuropathy, congenital hypomyelinating, 1, autosomal recessive 11.3
5 chronic inflammatory demyelinating polyneuropathy 10.5
6 polyneuropathy 10.5
7 demyelinating polyneuropathy 10.5
8 neuropathy 10.2
9 tremor 10.1
10 posttransplant acute limbic encephalitis 10.1
11 early-onset glaucoma 9.8 MTMR2 SBF2
12 charcot-marie-tooth disease, type 4b3 9.8 MTMR2 SBF2
13 charcot-marie-tooth disease, demyelinating, type 4f 9.8 MTMR2 SBF2
14 spinocerebellar ataxia type 1 with axonal neuropathy 9.7 MTMR2 SBF2
15 charcot-marie-tooth disease, type 4b2 9.7 MTMR2 SBF2
16 yunis-varon syndrome 9.7 FIG4 PIKFYVE VAC14
17 charcot-marie-tooth disease, type 4a 9.7 MTMR2 SBF2
18 charcot-marie-tooth disease, type 4b1 9.6 MTMR2 SBF2
19 charcot-marie-tooth disease, axonal, type 2e 9.5 MTMR2 SBF2

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



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

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

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

33 (show all 14)
# Description HPO Frequency HPO Source Accession
1 motor delay 33 occasional (7.5%) HP:0001270
2 gait disturbance 33 HP:0001288
3 decreased nerve conduction velocity 33 HP:0000762
4 decreased motor nerve conduction velocity 33 HP:0003431
5 areflexia 33 HP:0001284
6 hyporeflexia 33 HP:0001265
7 frequent falls 33 HP:0002359
8 ankle contracture 33 HP:0006466
9 distal muscle weakness 33 HP:0002460
10 distal sensory impairment 33 HP:0002936
11 axonal loss 33 HP:0003447
12 onion bulb formation 33 HP:0003383
13 distal arthrogryposis 33 HP:0005684
14 peripheral hypomyelination 33 HP:0007182

Symptoms via clinical synopsis from OMIM:

58
Neurologic Peripheral Nervous System:
areflexia
frequent falls
distal sensory impairment
onion bulb formation
gait difficulties
more
Skeletal Limbs:
ankle contractures

Neurologic Central Nervous System:
delayed motor development (in some patients)

Muscle Soft Tissue:
muscle amyotrophy

Clinical features from OMIM:

611228

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

47
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.35 FIG4 MTMR2 PIKFYVE SBF2 VAC14
2 nervous system MP:0003631 9.02 FIG4 MTMR2 PIKFYVE SBF2 VAC14

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

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Natural History Study of Charcot-Marie-Tooth 4J (CMT4J) Not yet recruiting NCT03810508

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

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

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

# Genetic test Affiliating Genes
1 Charcot-Marie-Tooth Disease, Type 4j 30 FIG4

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

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

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

# Title Authors Year
1
Charcot Marie Tooth disease type 4J with complex central nervous system features. ( 29468183 )
2018
2
A New Mutation in FIG4 Causes a Severe Form of CMT4J Involving TRPV4 in the Pathogenic Cascade. ( 28859335 )
2017
3
Loss of Fig4 in both Schwann cells and motor neurons contributes to CMT4J neuropathy. ( 25187576 )
2015
4
Whole exome sequencing identifies three recessive FIG4 mutations in an apparently dominant pedigree with Charcot-Marie-Tooth disease. ( 24878229 )
2014
5
Rapidly progressive asymmetrical weakness in Charcot-Marie-Tooth disease type 4J resembles chronic inflammatory demyelinating polyneuropathy. ( 23489662 )
2013
6
Distinctive genetic and clinical features of CMT4J: a severe neuropathy caused by mutations in the PI(3,5)P₂ phosphatase FIG4. ( 21705420 )
2011
7
Pathogenic mechanism of the FIG4 mutation responsible for Charcot-Marie-Tooth disease CMT4J. ( 21655088 )
2011
8
CMT4J: Charcot-Marie-Tooth disorder caused by mutations in FIG4. ( 18261132 )
2008
9
Mutation of FIG4 causes neurodegeneration in the pale tremor mouse and patients with CMT4J. ( 17572665 )
2007

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

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

76
# Symbol AA change Variation ID SNP ID
1 FIG4 p.Ile41Thr VAR_036974 rs121908287
2 FIG4 p.Leu17Pro VAR_071957 rs587777713
3 FIG4 p.Glu302Lys VAR_071958 rs587777714

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

6 (show all 28)
# Gene Variation Type Significance SNP ID Assembly Location
1 FIG4 NM_014845.5(FIG4): c.122T> C (p.Ile41Thr) single nucleotide variant Pathogenic rs121908287 GRCh37 Chromosome 6, 110036336: 110036336
2 FIG4 NM_014845.5(FIG4): c.122T> C (p.Ile41Thr) single nucleotide variant Pathogenic rs121908287 GRCh38 Chromosome 6, 109715133: 109715133
3 FIG4 NM_014845.5(FIG4): c.294delT (p.Phe98Leufs) deletion Pathogenic GRCh38 Chromosome 6, 109727113: 109727113
4 FIG4 NM_014845.5(FIG4): c.294delT (p.Phe98Leufs) deletion Pathogenic GRCh37 Chromosome 6, 110048316: 110048316
5 FIG4 NM_014845.5(FIG4): c.547C> T (p.Arg183Ter) single nucleotide variant Pathogenic rs121908288 GRCh37 Chromosome 6, 110056402: 110056402
6 FIG4 NM_014845.5(FIG4): c.547C> T (p.Arg183Ter) single nucleotide variant Pathogenic rs121908288 GRCh38 Chromosome 6, 109735199: 109735199
7 FIG4 NM_014845.5(FIG4): c.1043_1050delATCAGGCA (p.Asp348Glyfs) deletion Pathogenic GRCh38 Chromosome 6, 109743678: 109743685
8 FIG4 NM_014845.5(FIG4): c.1043_1050delATCAGGCA (p.Asp348Glyfs) deletion Pathogenic GRCh37 Chromosome 6, 110064881: 110064888
9 FIG4 NM_014845.5(FIG4): c.67-7T> C single nucleotide variant Benign/Likely benign rs56378532 GRCh37 Chromosome 6, 110036274: 110036274
10 FIG4 NM_014845.5(FIG4): c.67-7T> C single nucleotide variant Benign/Likely benign rs56378532 GRCh38 Chromosome 6, 109715071: 109715071
11 FIG4 NM_014845.5(FIG4): c.1090A> T (p.Met364Leu) single nucleotide variant Benign/Likely benign rs2295837 GRCh37 Chromosome 6, 110064928: 110064928
12 FIG4 NM_014845.5(FIG4): c.1090A> T (p.Met364Leu) single nucleotide variant Benign/Likely benign rs2295837 GRCh38 Chromosome 6, 109743725: 109743725
13 FIG4 NM_014845.5(FIG4): c.50T> C (p.Leu17Pro) single nucleotide variant Uncertain significance rs587777713 GRCh38 Chromosome 6, 109691485: 109691485
14 FIG4 NM_014845.5(FIG4): c.50T> C (p.Leu17Pro) single nucleotide variant Uncertain significance rs587777713 GRCh37 Chromosome 6, 110012688: 110012688
15 FIG4 NM_014845.5(FIG4): c.904G> A (p.Glu302Lys) single nucleotide variant Pathogenic rs587777714 GRCh37 Chromosome 6, 110064340: 110064340
16 FIG4 NM_014845.5(FIG4): c.904G> A (p.Glu302Lys) single nucleotide variant Pathogenic rs587777714 GRCh38 Chromosome 6, 109743137: 109743137
17 FIG4 NM_014845.5(FIG4): c.290-2A> T single nucleotide variant Pathogenic rs587777715 GRCh38 Chromosome 6, 109727107: 109727107
18 FIG4 NM_014845.5(FIG4): c.290-2A> T single nucleotide variant Pathogenic rs587777715 GRCh37 Chromosome 6, 110048310: 110048310
19 FIG4 NM_014845.5(FIG4): c.1141C> T (p.Arg381Ter) single nucleotide variant Pathogenic rs377357931 GRCh37 Chromosome 6, 110081456: 110081456
20 FIG4 NM_014845.5(FIG4): c.1141C> T (p.Arg381Ter) single nucleotide variant Pathogenic rs377357931 GRCh38 Chromosome 6, 109760253: 109760253
21 FIG4 NM_014845.5(FIG4): c.1948+3A> G single nucleotide variant Benign rs10499054 GRCh37 Chromosome 6, 110106234: 110106234
22 FIG4 NM_014845.5(FIG4): c.1948+3A> G single nucleotide variant Benign rs10499054 GRCh38 Chromosome 6, 109785031: 109785031
23 FIG4 NM_014845.5(FIG4): c.737G> A (p.Trp246Ter) single nucleotide variant Pathogenic/Likely pathogenic rs776005417 GRCh38 Chromosome 6, 109738415: 109738415
24 FIG4 NM_014845.5(FIG4): c.737G> A (p.Trp246Ter) single nucleotide variant Pathogenic/Likely pathogenic rs776005417 GRCh37 Chromosome 6, 110059618: 110059618
25 FIG4 NM_014845.5(FIG4): c.834A> T (p.Lys278Asn) single nucleotide variant Uncertain significance rs138048706 GRCh38 Chromosome 6, 109741502: 109741502
26 FIG4 NM_014845.5(FIG4): c.834A> T (p.Lys278Asn) single nucleotide variant Uncertain significance rs138048706 GRCh37 Chromosome 6, 110062705: 110062705
27 FIG4 NM_014845.5(FIG4): c.759delG (p.Phe254Serfs) deletion Pathogenic rs764717219 GRCh38 Chromosome 6, 109738437: 109738437
28 FIG4 NM_014845.5(FIG4): c.759delG (p.Phe254Serfs) deletion Pathogenic rs764717219 GRCh37 Chromosome 6, 110059640: 110059640

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

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

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

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

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.3 AK9 FIG4 MTMR2 PIKFYVE VAC14
2
Show member pathways
11.99 FIG4 MTMR2 PIKFYVE VAC14
3
Show member pathways
11.93 FIG4 MTMR2 PIKFYVE
4
Show member pathways
11.19 FIG4 MTMR2 PIKFYVE VAC14

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

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

# Name GO ID Score Top Affiliating Genes
1 intracellular membrane-bounded organelle GO:0043231 9.58 FIG4 MTMR2 VAC14
2 Golgi membrane GO:0000139 9.54 FIG4 PIKFYVE VAC14
3 endosome GO:0005768 9.46 FIG4 MTMR2 PIKFYVE VAC14
4 endosome membrane GO:0010008 9.43 FIG4 PIKFYVE VAC14
5 vacuolar membrane GO:0005774 9.32 MTMR2 SBF2
6 late endosome membrane GO:0031902 9.13 FIG4 PIKFYVE VAC14
7 early endosome membrane GO:0031901 8.92 FIG4 MTMR2 PIKFYVE VAC14

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

# Name GO ID Score Top Affiliating Genes
1 dephosphorylation GO:0016311 9.43 FIG4 MTMR2
2 neuron development GO:0048666 9.4 FIG4 MTMR2
3 phosphatidylinositol-3-phosphate biosynthetic process GO:0036092 9.37 FIG4 PIKFYVE
4 phosphatidylinositol metabolic process GO:0046488 9.33 FIG4 MTMR2 PIKFYVE
5 negative regulation of myelination GO:0031642 9.26 FIG4 MTMR2
6 phosphatidylinositol biosynthetic process GO:0006661 9.26 FIG4 MTMR2 PIKFYVE VAC14
7 protein tetramerization GO:0051262 9.02 SBF2
8 myelin assembly GO:0032288 8.8 FIG4 MTMR2 PIKFYVE

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

# Name GO ID Score Top Affiliating Genes
1 phosphatidylinositol-3-phosphatase activity GO:0004438 8.96 FIG4 MTMR2
2 phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity GO:0043813 8.62 FIG4 PIKFYVE

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

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
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39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
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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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