CMT2J
MCID: CHR657
MIFTS: 39

Charcot-Marie-Tooth Disease, Axonal, Type 2j (CMT2J)

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

Aliases & Classifications for Charcot-Marie-Tooth Disease, Axonal, Type 2j

MalaCards integrated aliases for Charcot-Marie-Tooth Disease, Axonal, Type 2j:

Name: Charcot-Marie-Tooth Disease, Axonal, Type 2j 56 52
Charcot-Marie-Tooth Disease Type 2j 12 52 29 6 15
Charcot-Marie-Tooth Disease, Type 2j 56 13 39 71
Cmt2j 56 12 58 73
Charcot-Marie-Tooth Disease, Type 2, with Hearing Loss and Pupillary Abnormalities 56 52
Charcot-Marie-Tooth Disease Type 2 with Hearing Loss and Pupillary Abnormalities 12 73
Charcot-Marie-Tooth Neuropathy Type 2j 12 73
Autosomal Dominant Charcot-Marie-Tooth Disease Type 2j 58
Charcot-Marie-Tooth Disease Neuronal Type 2j 73
Charcot-Marie-Tooth Disease Axonal Type 2j 73
Charcot-Marie-Tooth Neuropathy, Type 2j 56
Charcot Marie Tooth Disease Type 2j 52
Charcot-Marie-Tooth Disease 2j 73
Cmt 2j 52

Characteristics:

Orphanet epidemiological data:

58
autosomal dominant charcot-marie-tooth disease type 2j
Inheritance: Autosomal dominant; Age of onset: Adult;

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
usually begins in feet and legs (peroneal distribution)
upper limb involvement occurs later
onset in fourth to sixth decades
sensorineural hearing loss may be presenting feature


HPO:

31
charcot-marie-tooth disease, axonal, type 2j:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0110157
OMIM 56 607736
OMIM Phenotypic Series 56 PS118220
MeSH 43 D002607
ICD10 32 G60.0
ICD10 via Orphanet 33 G60.0
UMLS via Orphanet 72 C1843153
Orphanet 58 ORPHA99943
MedGen 41 C1843153
UMLS 71 C1843153

Summaries for Charcot-Marie-Tooth Disease, Axonal, Type 2j

UniProtKB/Swiss-Prot : 73 Charcot-Marie-Tooth disease 2J: A dominant axonal 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). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. Charcot-Marie-Tooth disease type 2J is characterized by the association of axonal peripheral neuropathy with hearing loss and pupillary abnormalities such as Adie pupil.

MalaCards based summary : Charcot-Marie-Tooth Disease, Axonal, Type 2j, also known as charcot-marie-tooth disease type 2j, is related to axonal neuropathy and polyneuropathy. An important gene associated with Charcot-Marie-Tooth Disease, Axonal, Type 2j is MPZ (Myelin Protein Zero). Affiliated tissues include eye, and related phenotypes are sensorineural hearing impairment and dysphagia

Disease Ontology : 12 A Charcot-Marie-Tooth disease type 2 characterized by hearing loss and pupillary abnormalities and has material basis in heterozygous mutation in the myelin protein-zero gene (MPZ) on chromosome 1q23.

OMIM : 56 For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210). (607736)

Related Diseases for Charcot-Marie-Tooth Disease, Axonal, Type 2j

Diseases in the Charcot-Marie-Tooth Disease, Axonal, Type 2e family:

Charcot-Marie-Tooth Disease, Axonal, Type 2a1 Charcot-Marie-Tooth Disease, Axonal, Type 2b
Charcot-Marie-Tooth Disease, Axonal, Type 2d Charcot-Marie-Tooth Disease, Axonal, Type 2b1
Charcot-Marie-Tooth Disease, Axonal, Type 2b2 Charcot-Marie-Tooth Disease, Axonal, Type 2f
Charcot-Marie-Tooth Disease, Axonal, Type 2i Charcot-Marie-Tooth Disease, Axonal, Type 2h
Charcot-Marie-Tooth Disease, Axonal, Type 2j Charcot-Marie-Tooth Disease, Axonal, Type 2k
Charcot-Marie-Tooth Disease, Axonal, Type 2l Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type 2a2a
Charcot-Marie-Tooth Disease, Axonal, Type 2n Charcot-Marie-Tooth Disease, Axonal, Type 2o
Charcot-Marie-Tooth Disease, Axonal, Type 2p Charcot-Marie-Tooth Disease, Axonal, Type 2q
Charcot-Marie-Tooth Disease, Axonal, Type 2r Charcot-Marie-Tooth Disease, Axonal, Type 2u
Charcot-Marie-Tooth Disease, Axonal, Type 2v Charcot-Marie-Tooth Disease, Axonal, Type 2w
Charcot-Marie-Tooth Disease, Axonal, Type 2x Charcot-Marie-Tooth Disease, Axonal, Type 2z
Charcot-Marie-Tooth Disease, Axonal, Type 2cc Charcot-Marie-Tooth Disease, Axonal, Type 2t
Charcot-Marie-Tooth Disease, Axonal, Autosomal Recessive, Type 2a2b Charcot-Marie-Tooth Disease, Axonal, Type 2dd
Charcot-Marie-Tooth Disease, Axonal, Type 2ee Autosomal Recessive Axonal Charcot-Marie-Tooth Disease Due to Copper Metabolism Defect

Diseases related to Charcot-Marie-Tooth Disease, Axonal, Type 2j via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 75)
# Related Disease Score Top Affiliating Genes
1 axonal neuropathy 30.3 NEFL GDAP1 GARS1
2 polyneuropathy 29.7 SH3TC2 PRX MPZ GDAP1 EGR2
3 charcot-marie-tooth disease 26.9 SH3TC2 SBF2 PRX NEFL MTMR2 MPZ
4 tooth disease 26.9 SH3TC2 SBF2 PRX NEFL MTMR2 MPZ
5 adie pupil 11.8
6 branchiootic syndrome 1 10.5
7 pure autonomic failure 10.5
8 autonomic dysfunction 10.5
9 charcot-marie-tooth disease, axonal, type 2w 10.2 MPZ GDAP1
10 mononeuropathy 10.2 SH3TC2 MPZ
11 nerve compression syndrome 10.2 SH3TC2 MPZ
12 charcot-marie-tooth disease type 5 10.0 PRX GARS1
13 charcot-marie-tooth disease, dominant intermediate a 10.0 PRX MPZ GDAP1
14 distal hereditary motor neuronopathy type 2 10.0 MPZ GARS1
15 charcot-marie-tooth disease, x-linked recessive, 2 10.0 MPZ EGR2
16 peripheral demyelinating neuropathy, central dysmyelination, waardenburg syndrome, and hirschsprung disease 10.0 MPZ EGR2
17 early-onset glaucoma 10.0 SBF2 MTMR2
18 carpal tunnel syndrome 9.9 SH3TC2 MPZ
19 corneal dystrophy, fleck 9.9 SBF2 MTMR2
20 hereditary neuropathies 9.9 PRX MTMR2 MPZ
21 neuronopathy, distal hereditary motor, type va 9.9 GDAP1 GARS1
22 autosomal dominant distal hereditary motor neuronopathy 9.9 SH3TC2 MPZ GARS1
23 charcot-marie-tooth disease, dominant intermediate c 9.9 MPZ GDAP1 GARS1
24 myopathy, centronuclear, x-linked 9.9 SBF2 MTMR2
25 motor peripheral neuropathy 9.8 SH3TC2 GARS1
26 charcot-marie-tooth disease, axonal, type 2t 9.8 SH3TC2 SBF2 GDAP1
27 argyll robertson pupil 9.8 MPZ GDAP1 EGR2
28 pupil disease 9.8 MPZ GDAP1 EGR2
29 abnormal pupillary function 9.8 MPZ GDAP1 EGR2
30 neuropathy, hereditary motor and sensory, russe type 9.8 SH3TC2 GDAP1 EGR2
31 hereditary sensory neuropathy 9.8 MPZ GDAP1
32 yunis-varon syndrome 9.7 SBF2 MTMR2 GDAP1
33 hereditary paraganglioma-pheochromocytoma syndromes 9.7 MPZ KIF1B
34 charcot-marie-tooth disease, dominant intermediate d 9.7 SH3TC2 MPZ KIF1B
35 genetic motor neuron disease 9.6 SH3TC2 NEFL MPZ GARS1
36 motor neuron disease 9.6 SH3TC2 NEFL MPZ GARS1
37 charcot-marie-tooth disease, axonal, type 2n 9.5 KIF1B GDAP1 GARS1
38 charcot-marie-tooth disease, dominant intermediate e 9.3 SH3TC2 SBF2 MTMR2 MPZ GDAP1
39 charcot-marie-tooth disease, type 4b3 9.3 SH3TC2 SBF2 MTMR2 MPZ GDAP1
40 charcot-marie-tooth disease, dominant intermediate b 9.3 SH3TC2 SBF2 MTMR2 MPZ GDAP1
41 charcot-marie-tooth disease, axonal, type 2a1 9.3 MPZ KIF1B GDAP1 GARS1
42 charcot-marie-tooth disease, type 4h 9.1 SH3TC2 SBF2 PRX MTMR2 MPZ GDAP1
43 charcot-marie-tooth disease, type 4j 9.1 SH3TC2 SBF2 PRX MTMR2 MPZ GDAP1
44 charcot-marie-tooth disease, type 4b2 9.1 SH3TC2 SBF2 PRX MTMR2 MPZ GDAP1
45 charcot-marie-tooth disease, type 4b1 9.1 SH3TC2 SBF2 PRX MTMR2 MPZ GDAP1
46 charcot-marie-tooth disease intermediate type 9.0 SH3TC2 SBF2 MTMR2 MPZ GDAP1 GARS1
47 charcot-marie-tooth disease, axonal, type 2l 9.0 NEFL MPZ KIF1B GDAP1 GARS1
48 charcot-marie-tooth disease, axonal, type 2f 9.0 NEFL MPZ KIF1B GDAP1 GARS1
49 charcot-marie-tooth disease, axonal, type 2b2 9.0 NEFL MPZ KIF1B GDAP1 GARS1
50 spinal muscular atrophy 8.9 SH3TC2 PRX NEFL KIF1B GARS1

Graphical network of the top 20 diseases related to Charcot-Marie-Tooth Disease, Axonal, Type 2j:



Diseases related to Charcot-Marie-Tooth Disease, Axonal, Type 2j

Symptoms & Phenotypes for Charcot-Marie-Tooth Disease, Axonal, Type 2j

Human phenotypes related to Charcot-Marie-Tooth Disease, Axonal, Type 2j:

31 (show all 15)
# Description HPO Frequency HPO Source Accession
1 sensorineural hearing impairment 31 HP:0000407
2 dysphagia 31 HP:0002015
3 abnormality of the eye 31 HP:0000478
4 areflexia 31 HP:0001284
5 pes cavus 31 HP:0001761
6 hyporeflexia 31 HP:0001265
7 abnormality of the respiratory system 31 HP:0002086
8 steppage gait 31 HP:0003376
9 distal amyotrophy 31 HP:0003693
10 distal muscle weakness 31 HP:0002460
11 distal sensory impairment 31 HP:0002936
12 progressive sensorineural hearing impairment 31 HP:0000408
13 foot dorsiflexor weakness 31 HP:0009027
14 peripheral demyelination 31 HP:0011096
15 axonal degeneration/regeneration 31 HP:0003378

Symptoms via clinical synopsis from OMIM:

56
Abdomen Gastrointestinal:
dysphagia

Skeletal Feet:
pes cavus

Head And Neck Eyes:
slow pupillary reaction with slow light convergence reflex
absent pupillary reaction

Neurologic Peripheral Nervous System:
areflexia
hyporeflexia
distal sensory impairment
distal limb muscle weakness due to peripheral neuropathy
distal limb muscle atrophy due to peripheral neuropathy
more
Head And Neck Ears:
deafness
sensorineural hearing loss, progressive
brainstem auditory evoked potentials (baeps) suggest peripheral lesion

Respiratory:
coughing spasms, recurrent (reported in 1 family)

Clinical features from OMIM:

607736

GenomeRNAi Phenotypes related to Charcot-Marie-Tooth Disease, Axonal, Type 2j according to GeneCards Suite gene sharing:

26 (show all 12)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-105 9.44 GARS1 KIF1B
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-132 9.44 GARS1
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-153 9.44 KIF1B
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-157 9.44 GARS1
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-165 9.44 KIF1B
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-177 9.44 GARS1
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-199 9.44 GARS1
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-211 9.44 KIF1B
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-214 9.44 GARS1
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-41 9.44 GARS1
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-67 9.44 GARS1
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-87 9.44 GARS1

MGI Mouse Phenotypes related to Charcot-Marie-Tooth Disease, Axonal, Type 2j:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.65 EGR2 GARS1 GDAP1 KIF1B MPZ MTMR2
2 nervous system MP:0003631 9.32 EGR2 GARS1 GDAP1 KIF1B MPZ MTMR2

Drugs & Therapeutics for Charcot-Marie-Tooth Disease, Axonal, Type 2j

Search Clinical Trials , NIH Clinical Center for Charcot-Marie-Tooth Disease, Axonal, Type 2j

Genetic Tests for Charcot-Marie-Tooth Disease, Axonal, Type 2j

Genetic tests related to Charcot-Marie-Tooth Disease, Axonal, Type 2j:

# Genetic test Affiliating Genes
1 Charcot-Marie-Tooth Disease Type 2j 29 MPZ

Anatomical Context for Charcot-Marie-Tooth Disease, Axonal, Type 2j

MalaCards organs/tissues related to Charcot-Marie-Tooth Disease, Axonal, Type 2j:

40
Eye

Publications for Charcot-Marie-Tooth Disease, Axonal, Type 2j

Articles related to Charcot-Marie-Tooth Disease, Axonal, Type 2j:

(show all 14)
# Title Authors PMID Year
1
Late-onset Charcot-Marie-Tooth type 2 disease with hearing impairment associated with a novel Pro105Thr mutation in the MPZ gene. 56 6
17663472 2007
2
Case records of the Massachusetts General Hospital. Case 18-2006. A 57-year-old woman with numbness and weakness of the feet and legs. 56 6
16775239 2006
3
Hearing loss as the first feature of late-onset axonal CMT disease due to a novel P0 mutation. 56 6
15326256 2004
4
Chronic cough due to Thr124Met mutation in the peripheral myelin protein zero (MPZ gene). 6 56
15159512 2004
5
An axonal form of Charcot-Marie-Tooth disease showing distinctive features in association with mutations in the peripheral myelin protein zero gene (Thr124Met or Asp75Val). 56 6
11080237 2000
6
Axonal phenotype of Charcot-Marie-Tooth disease associated with a mutation in the myelin protein zero gene. 56 6
10329755 1999
7
The Thr124Met mutation in the peripheral myelin protein zero (MPZ) gene is associated with a clinically distinct Charcot-Marie-Tooth phenotype. 56 6
10071056 1999
8
Charcot-Marie-Tooth neuropathy type 2 and P0 point mutations: two novel amino acid substitutions (Asp61Gly; Tyr119Cys) and a possible "hotspot" on Thr124Met. 6
10764043 2000
9
Charcot-Marie-Tooth Neuropathy Type 2 – ARCHIVED CHAPTER, FOR HISTORICAL REFERENCE ONLY 6
20301462 1998
10
Charcot-Marie-Tooth (CMT) Hereditary Neuropathy Overview 6
20301532 1998
11
Mutations of the same sequence of the myelin P0 gene causing two different phenotypes. 6
9452091 1998
12
Parasympathetic Dominant Autonomic Dysfunction in Charcot-Marie-Tooth Disease Type 2J with the MPZ Thr124Met Mutation. 61
26234237 2015
13
Charcot–Marie–Tooth disease type 2J with MPZ Thr124Met mutation: clinico-electrophysiological and MRI study of a family. 61
19629567 2009
14
A new locus for autosomal dominant Charcot-Marie-Tooth disease type 2 (CMT2L) maps to chromosome 12q24. 61
15021985 2004

Variations for Charcot-Marie-Tooth Disease, Axonal, Type 2j

ClinVar genetic disease variations for Charcot-Marie-Tooth Disease, Axonal, Type 2j:

6 (show all 12) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 MPZ NM_000530.8(MPZ):c.499G>C (p.Gly167Arg)SNV Pathogenic 14170 rs121913586 1:161276204-161276204 1:161306414-161306414
2 MPZ NM_000530.8(MPZ):c.371C>T (p.Thr124Met)SNV Pathogenic 14181 rs121913595 1:161276575-161276575 1:161306785-161306785
3 MPZ NM_000530.8(MPZ):c.224A>T (p.Asp75Val)SNV Pathogenic 14184 rs121913597 1:161277058-161277058 1:161307268-161307268
4 MPZ NM_000530.8(MPZ):c.434A>C (p.Tyr145Ser)SNV Pathogenic 14191 rs121913603 1:161276512-161276512 1:161306722-161306722
5 MPZ NM_000530.8(MPZ):c.290A>T (p.Glu97Val)SNV Pathogenic 14195 rs121913606 1:161276656-161276656 1:161306866-161306866
6 MPZ NM_000530.8(MPZ):c.397C>A (p.Pro133Thr)SNV Pathogenic/Likely pathogenic 462797 rs1553259648 1:161276549-161276549 1:161306759-161306759
7 MPZ NM_000530.8(MPZ):c.313C>A (p.Pro105Thr)SNV Likely pathogenic 14199 rs121913609 1:161276633-161276633 1:161306843-161306843
8 MPZ NM_000530.8(MPZ):c.703_705AAG[1] (p.Lys236del)short repeat Conflicting interpretations of pathogenicity 447734 rs755446743 1:161275705-161275707 1:161305915-161305917
9 MPZ NM_000530.8(MPZ):c.451C>A (p.Pro151Thr)SNV Conflicting interpretations of pathogenicity 216963 1:161276252-161276252 1:161306462-161306462
10 MPZ NM_000530.8(MPZ):c.133C>T (p.Arg45Trp)SNV Uncertain significance 246524 rs200151353 1:161277149-161277149 1:161307359-161307359
11 MPZ NM_000530.8(MPZ):c.684C>T (p.Ser228=)SNV Benign/Likely benign 129619 rs34307129 1:161275729-161275729 1:161305939-161305939
12 MPZ NM_000530.8(MPZ):c.600G>A (p.Gly200=)SNV Benign 138242 rs16832790 1:161275943-161275943 1:161306153-161306153

UniProtKB/Swiss-Prot genetic disease variations for Charcot-Marie-Tooth Disease, Axonal, Type 2j:

73
# Symbol AA change Variation ID SNP ID
1 MPZ p.Thr124Met VAR_004529 rs121913595
2 MPZ p.Asp75Val VAR_015973 rs121913597
3 MPZ p.Glu97Val VAR_029975 rs121913606

Expression for Charcot-Marie-Tooth Disease, Axonal, Type 2j

Search GEO for disease gene expression data for Charcot-Marie-Tooth Disease, Axonal, Type 2j.

Pathways for Charcot-Marie-Tooth Disease, Axonal, Type 2j

GO Terms for Charcot-Marie-Tooth Disease, Axonal, Type 2j

Cellular components related to Charcot-Marie-Tooth Disease, Axonal, Type 2j according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 axon cytoplasm GO:1904115 9.16 NEFL KIF1B
2 axon GO:0030424 9.02 SBF2 NEFL MTMR2 KIF1B GARS1
3 vacuolar membrane GO:0005774 8.96 SBF2 MTMR2

Biological processes related to Charcot-Marie-Tooth Disease, Axonal, Type 2j according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 anterograde axonal transport GO:0008089 9.16 NEFL KIF1B
2 peripheral nervous system myelin maintenance GO:0032287 8.96 SH3TC2 PRX
3 myelination GO:0042552 8.8 SBF2 MPZ EGR2

Sources for Charcot-Marie-Tooth Disease, Axonal, Type 2j

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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