Details of Disease

General Information of Disease (ID: DISSRZG7)

• Disease Name: Charcot-Marie-Tooth disease type 1A
• Synonyms: CMT 1A; Charcot Marie Tooth disease type 1A; Charcot-Marie-Tooth neuropathy, type 1A; HMSN 1A; Charcot-Marie-Tooth disease, demyelinating, type 1A; Charcot-Marie-Tooth disease, autosomal dominant, with focally folded myelin sheaths, type 1A; Charcot-Marie-Tooth disease, type 1A; autosomal dominant Charcot-Marie-Tooth disease with focally folded myelin sheaths type 1A; HMSN1A; CMT1A; microduplication 17p12; hereditary motor and sensory neuropathy 1A; Charcot-Marie-Tooth disease type 1A; Charcot-Marie-Tooth neuropathy type 1A; Charcot-Marie-Tooth syndrome type 1A
• Definition: Charcot-Marie-Tooth disease type 1A (CMT1A) is a type ofinherited neurological disorder that affects the peripheral nerves. Affected individuals experience weakness and wasting (atrophy) of the muscles of the lower legs beginning in adolescence; later they experience hand weakness and sensory loss. CMT1A is caused byhaving an extra copy (a duplication) of the PMP22 gene. It is inherited in an autosomal dominant manner. Treatment for this condition may include physical therapy ; occupational therapy ; braces and other orthopedic devices; orthopedic surgery;and pain medications.
• Disease Hierarchy:
  DISLH99V: Partial duplication of the short arm of chromosome 17
  DIS56F9A: Charcot-Marie-Tooth disease type 1
  DISSRZG7: Charcot-Marie-Tooth disease type 1A
• Disease Identifiers:
  MONDO ID: MONDO_0007309
  MESH ID: D002607
  UMLS CUI: C0270911
  OMIM ID: 118220
  MedGen ID: 75727
  Orphanet ID: 101081
  SNOMED CT ID: 40632002

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 5 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
GJB1	TTSJIRP	Strong	Genetic Variation	[1]
MAG	TT9XFON	Strong	Biomarker	[2]
NTF3	TTZHKV9	Strong	Biomarker	[3]
RNMT	TTG45HY	Strong	Genetic Variation	[4]
TRPV4	TTKP2SU	Strong	Biomarker	[5]

This Disease Is Related to 18 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
LITAF	OTT5JX1F	Limited	Genetic Variation	[6]
SIPA1L2	OT8NJE5D	Limited	Biomarker	[7]
SLC25A46	OTFEV9SV	Disputed	Biomarker	[8]
CADM4	OT0TFMFE	Strong	Biomarker	[2]
CHCHD2	OTL5PA3Y	Strong	Genetic Variation	[9]
COX10	OTCYIS0L	Strong	Biomarker	[10]
DSCAM	OTL7PRMK	Strong	Genetic Variation	[6]
FIG4	OT501PY9	Strong	Biomarker	[11]
HOXD10	OT0NOWU2	Strong	Biomarker	[12]
KIF1B	OTI1XQTO	Strong	Biomarker	[13]
LRSAM1	OTOKWR6C	Strong	Biomarker	[14]
MLXIP	OT30UNI7	Strong	Genetic Variation	[15]
MORC2	OT52A8BJ	Strong	Biomarker	[16]
MPZ	OTAR2YXH	Strong	Genetic Variation	[4]
PXMP2	OTYHX5MI	Strong	Biomarker	[17]
RAI1	OTKLQU00	Strong	Genetic Variation	[18]
RER1	OTTBAUBP	Strong	Genetic Variation	[19]
PMP22	OTXWYWCZ	Definitive	Autosomal dominant	[20]

References

• [1] X-linked Charcot-Marie-Tooth disease predominates in a cohort of multiethnic Malaysian patients.Muscle Nerve. 2014 Feb;49(2):198-201. doi: 10.1002/mus.23892. Epub 2013 Oct 4.
• [2] An essential role of MAG in mediating axon-myelin attachment in Charcot-Marie-Tooth 1A disease.Neurobiol Dis. 2013 Jan;49:221-31. doi: 10.1016/j.nbd.2012.08.009. Epub 2012 Aug 25.
• [3] AAV1.NT-3 gene therapy for charcot-marie-tooth neuropathy.Mol Ther. 2014 Mar;22(3):511-521. doi: 10.1038/mt.2013.250. Epub 2013 Oct 28.
• [4] New polymorphic short tandem repeats for PCR-based Charcot-Marie-Tooth disease type 1A duplication diagnosis.Clin Chem. 2001 May;47(5):838-43.
• [5] Axonal neuropathy-associated TRPV4 regulates neurotrophic factor-derived axonal growth.J Biol Chem. 2012 Feb 17;287(8):6014-24. doi: 10.1074/jbc.M111.316315. Epub 2011 Dec 20.
• [6] Modifier Gene Candidates in Charcot-Marie-Tooth Disease Type 1A: A Case-Only Genome-Wide Association Study.J Neuromuscul Dis. 2019;6(2):201-211. doi: 10.3233/JND-190377.
• [7] Variation in SIPA1L2 is correlated with phenotype modification in Charcot- Marie- Tooth disease type 1A.Ann Neurol. 2019 Mar;85(3):316-330. doi: 10.1002/ana.25426.
• [8] Mutations in SLC25A46, encoding a UGO1-like protein, cause an optic atrophy spectrum disorder. Nat Genet. 2015 Aug;47(8):926-32. doi: 10.1038/ng.3354. Epub 2015 Jul 13.
• [9] Abl2 kinase phosphorylates Bi-organellar regulator MNRR1 in mitochondria, stimulating respiration.Biochim Biophys Acta Mol Cell Res. 2017 Feb;1864(2):440-448. doi: 10.1016/j.bbamcr.2016.11.029. Epub 2016 Nov 30.
• [10] Improved testing for CMT1A and HNPP using multiplex ligation-dependent probe amplification (MLPA) with rapid DNA preparations: comparison with the interphase FISH method.Hum Mutat. 2004 Aug;24(2):164-71. doi: 10.1002/humu.20072.
• [11] 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.
• [12] 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.
• [13] Characterization of Charcot-Marie-Tooth optic neuropathy.J Neurol. 2017 Dec;264(12):2431-2435. doi: 10.1007/s00415-017-8645-2. Epub 2017 Oct 23.
• [14] 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.
• [15] Association of miR-149 polymorphism with onset age and severity in Charcot-Marie-Tooth disease type 1A.Neuromuscul Disord. 2018 Jun;28(6):502-507. doi: 10.1016/j.nmd.2018.04.002. Epub 2018 Apr 11.
• [16] 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.
• [17] A novel point mutation in the peripheral myelin protein 22 (PMP22) gene associated with Charcot-Marie-Tooth disease type 1A.Neurology. 1997 Feb;48(2):489-93. doi: 10.1212/wnl.48.2.489.
• [18] Nonrecurrent 17p11.2p12 Rearrangement Events that Result in Two Concomitant Genomic Disorders: The PMP22-RAI1 Contiguous Gene Duplication Syndrome.Am J Hum Genet. 2015 Nov 5;97(5):691-707. doi: 10.1016/j.ajhg.2015.10.003.
• [19] Rer1 and calnexin regulate endoplasmic reticulum retention of a peripheral myelin protein 22 mutant that causes type 1A Charcot-Marie-Tooth disease.Sci Rep. 2014 Nov 11;4:6992. doi: 10.1038/srep06992.
• [20] 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.