Details of Disease

Disease Name

Charcot-Marie-Tooth disease type 2

autosomal dominant Charcot-Marie-Tooth disease type 2; Charcot-Marie-Tooth type 2; hereditary motor and sensory neuropathy Guadalajara neuronal type; hereditary motor and sensory neuropathy type 2; CMT2; autosomal dominant axonal Charcot-Marie-Tooth disease; hereditary motor and sensory neuropathy Okinawa type

Definition

A Charcot-Marie-Tooth disease characterized by abnormalities in the axon of the peripheral nerve cell.

Disease Hierarchy

DIS3BT2L: Charcot marie tooth disease

DISR30O9: Charcot-Marie-Tooth disease type 2

Disease Identifiers

MONDO ID

MONDO_0018993

MESH ID

D002607

UMLS CUI

C0270914

MedGen ID

124378

Orphanet ID

64746

SNOMED CT ID

398187000

General Information of Disease (ID: DISR30O9)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 9 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
DNM2	TTVRA5G	Strong	Genetic Variation	[1]
HSPB8	TTY0OJN	Strong	Genetic Variation	[2]
KIF5A	TTCJPAH	Strong	Genetic Variation	[3]
RAB7A	TTF6WAQ	Strong	Biomarker	[4]
SCN9A	TT4G2JS	Strong	GermlineCausalMutation	[5]
TRPV4	TTKP2SU	Strong	Biomarker	[6]
VCP	TTHNLSB	Strong	Genetic Variation	[7]
WNK1	TTJ9UMX	Strong	Genetic Variation	[8]
RAB7A	TTF6WAQ	Definitive	Autosomal dominant	[9]
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⏷ Show the Full List of 9 DTT(s)

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
HINT1	DEWJATF	Definitive	Genetic Variation	[10]
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This Disease Is Related to 24 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
BSCL2	OT73V6Y4	Limited	Genetic Variation	[11]
MFN2	OTPYN8A3	Limited	Genetic Variation	[12]
SLC25A46	OTFEV9SV	Limited	Genetic Variation	[13]
AARS1	OTW8D813	Strong	CausalMutation	[14]
AIFM1	OTKPWB7Q	Strong	Biomarker	[4]
DHTKD1	OTDQLSNT	Strong	Genetic Variation	[15]
DNAJB2	OTZHPV5M	Strong	Genetic Variation	[16]
FIG4	OT501PY9	Strong	Biomarker	[17]
GARS1	OT5B6R9Y	Strong	Genetic Variation	[18]
HOXD10	OT0NOWU2	Strong	Biomarker	[19]
IGHMBP2	OTAZFPF5	Strong	Genetic Variation	[20]
KIF1A	OT3JVEGV	Strong	Biomarker	[21]
KIF1B	OTI1XQTO	Strong	Biomarker	[4]
LRSAM1	OTOKWR6C	Strong	Biomarker	[22]
MAD2L1BP	OT2O2IUJ	Strong	Biomarker	[23]
MORC2	OT52A8BJ	Strong	Biomarker	[24]
RETREG1	OTYOSLZX	Strong	Biomarker	[25]
SPTLC1	OTN0Z98K	Strong	Biomarker	[26]
TFG	OT2KJENI	Strong	Genetic Variation	[27]
CHCHD10	OTCDHAM6	Definitive	Biomarker	[28]
GDAP1	OTQE1O25	Definitive	Genetic Variation	[29]
NEFL	OTQESJV4	Definitive	Autosomal recessive	[9]
NLN	OTFRITPU	Definitive	Genetic Variation	[30]
RAB7A	OTBSPWMQ	Definitive	Autosomal dominant	[9]
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⏷ Show the Full List of 24 DOT(s)

References

1	Magnetic resonance imaging findings of leg musculature in Charcot-Marie-Tooth disease type 2 due to dynamin 2 mutation.J Neurol. 2008 Jul;255(7):986-92. doi: 10.1007/s00415-008-0808-8. Epub 2008 Jun 17.
2	Small heat shock protein B3 (HSPB3) mutation in an axonal Charcot-Marie-Tooth disease family.J Peripher Nerv Syst. 2018 Mar;23(1):60-66. doi: 10.1111/jns.12249. Epub 2018 Feb 6.
3	Hot-spot KIF5A mutations cause familial ALS. Brain. 2018 Mar 1;141(3):688-697. doi: 10.1093/brain/awx370.
4	A novel type of hereditary motor and sensory neuropathy characterized by a mild phenotype.Arch Neurol. 1999 Oct;56(10):1283-8. doi: 10.1001/archneur.56.10.1283.
5	Hereditary sensory and autonomic neuropathy type IID caused by an SCN9A mutation. Neurology. 2013 Apr 30;80(18):1641-9. doi: 10.1212/WNL.0b013e3182904fdd. Epub 2013 Apr 17.
6	Incidence and Clinical Features of TRPV4-Linked Axonal Neuropathies in a USA Cohort of Charcot-Marie-Tooth Disease Type 2.Neuromolecular Med. 2020 Mar;22(1):68-72. doi: 10.1007/s12017-019-08564-4. Epub 2019 Aug 29.
7	Clinical spectrum of valosin containing protein (VCP)-opathy.Muscle Nerve. 2016 Jun;54(1):94-9. doi: 10.1002/mus.24980. Epub 2015 Dec 29.
8	Arthropathy-related pain in a patient with congenital impairment of pain sensation due to hereditary sensory and autonomic neuropathy type II with a rare mutation in the WNK1/HSN2 gene: a case report.BMC Neurol. 2016 Oct 21;16(1):201. doi: 10.1186/s12883-016-0727-8.
9	Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
10	Whole exome sequencing reveals a broader variant spectrum of Charcot-Marie-Tooth disease type 2.Neurogenetics. 2020 Apr;21(2):79-86. doi: 10.1007/s10048-019-00591-4. Epub 2019 Dec 12.
11	Clinical and Molecular Characterization of BSCL2 Mutations in a Taiwanese Cohort with Hereditary Neuropathy.PLoS One. 2016 Jan 27;11(1):e0147677. doi: 10.1371/journal.pone.0147677. eCollection 2016.
12	Enhancing folic acid metabolism suppresses defects associated with loss of Drosophila mitofusin.Cell Death Dis. 2019 Mar 25;10(4):288. doi: 10.1038/s41419-019-1496-2.
13	Reduction of Rpd3 suppresses defects in locomotive ability and neuronal morphology induced by the knockdown of Drosophila SLC25A46 via an epigenetic pathway.Exp Cell Res. 2019 Dec 15;385(2):111673. doi: 10.1016/j.yexcr.2019.111673. Epub 2019 Oct 12.
14	Hypermorphic and hypomorphic AARS alleles in patients with CMT2N expand clinical and molecular heterogeneities.Hum Mol Genet. 2018 Dec 1;27(23):4036-4050. doi: 10.1093/hmg/ddy290.
15	A nonsense mutation in DHTKD1 causes Charcot-Marie-Tooth disease type 2 in a large Chinese pedigree. Am J Hum Genet. 2012 Dec 7;91(6):1088-94. doi: 10.1016/j.ajhg.2012.09.018. Epub 2012 Nov 8.
16	HSJ1-related hereditary neuropathies: novel mutations and extended clinical spectrum. Neurology. 2014 Nov 4;83(19):1726-32. doi: 10.1212/WNL.0000000000000966. Epub 2014 Oct 1.
17	Mutation of FIG4 causes neurodegeneration in the pale tremor mouse and patients with CMT4J. Nature. 2007 Jul 5;448(7149):68-72. doi: 10.1038/nature05876. Epub 2007 Jun 17.
18	Dimerization is required for GARS-mediated neurotoxicity in dominant CMT disease.Hum Mol Genet. 2016 Apr 15;25(8):1528-42. doi: 10.1093/hmg/ddw031. Epub 2016 Feb 7.
19	A HOX gene mutation in a family with isolated congenital vertical talus and Charcot-Marie-Tooth disease. Am J Hum Genet. 2004 Jul;75(1):92-6. doi: 10.1086/422015. Epub 2004 May 14.
20	IGHMBP2-related clinical and genetic features in a cohort of Chinese Charcot-Marie-Tooth disease type 2 patients.Neuromuscul Disord. 2017 Feb;27(2):193-199. doi: 10.1016/j.nmd.2016.11.008. Epub 2016 Nov 18.
21	De novo mutations in the motor domain of KIF1A cause cognitive impairment, spastic paraparesis, axonal neuropathy, and cerebellar atrophy. Hum Mutat. 2015 Jan;36(1):69-78. doi: 10.1002/humu.22709. Epub 2014 Nov 27.
22	Mutation in the gene encoding ubiquitin ligase LRSAM1 in patients with Charcot-Marie-Tooth disease. PLoS Genet. 2010 Aug 26;6(8):e1001081. doi: 10.1371/journal.pgen.1001081.
23	Charcot-Marie-Tooth disease type 2 associated with mutation of the myelin protein zero gene.Neurology. 1998 May;50(5):1397-401. doi: 10.1212/wnl.50.5.1397.
24	Hyperactivation of HUSH complex function by Charcot-Marie-Tooth disease mutation in MORC2.Nat Genet. 2017 Jul;49(7):1035-1044. doi: 10.1038/ng.3878. Epub 2017 Jun 5.
25	Mutations in FAM134B, encoding a newly identified Golgi protein, cause severe sensory and autonomic neuropathy. Nat Genet. 2009 Nov;41(11):1179-81. doi: 10.1038/ng.464. Epub 2009 Oct 18.
26	Hereditary sensory neuropathy type 1 is caused by the accumulation of two neurotoxic sphingolipids.J Biol Chem. 2010 Apr 9;285(15):11178-87. doi: 10.1074/jbc.M109.092973. Epub 2010 Jan 22.
27	A novel TFG mutation causes Charcot-Marie-Tooth disease type 2 and impairs TFG function. Neurology. 2014 Sep 2;83(10):903-12. doi: 10.1212/WNL.0000000000000758. Epub 2014 Aug 6.
28	CHCHD10 mutations promote loss of mitochondrial cristae junctions with impaired mitochondrial genome maintenance and inhibition of apoptosis.EMBO Mol Med. 2016 Jan 1;8(1):58-72. doi: 10.15252/emmm.201505496.
29	A novel autosomal dominant GDAP1 mutation in an Italian CMT2 family.J Peripher Nerv Syst. 2012 Sep;17(3):351-5. doi: 10.1111/j.1529-8027.2012.00414.x.
30	Evaluation of Respiratory Muscle Strength and Pulmonary Function in Patients with Charcot-Marie-Tooth Disease Type 2.Eur Neurol. 2015;74(5-6):310-4. doi: 10.1159/000442282. Epub 2015 Dec 17.