Details of Disease

Disease Name

Hereditary motor and sensory neuropathy

Definition

A group of slowly progressive inherited disorders affecting motor and sensory peripheral nerves. Subtypes include HMSNs I-VII. HMSN I and II both refer to CHARCOT-MARIE-Tooth DISEASE. HMSN III refers to hypertrophic neuropathy of infancy. HMSN IV refers to REFSUM DISEASE. HMSN V refers to a condition marked by a hereditary motor and sensory neuropathy associated with spastic paraplegia (see SPASTIC PARAPLEGIA, HEREDITARY). HMSN VI refers to HMSN associated with an inherited optic atrophy (OPTIC ATROPHIES, HEREDITARY), and HMSN VII refers to HMSN associated with retinitis pigmentosa. (From Adams et al., Principles of Neurology, 6th ed, p1343)

Disease Hierarchy

DISSYRHC: Hereditary peripheral neuropathy

DISR0X2K: Hereditary motor and sensory neuropathy

Disease Identifiers

MONDO ID

MONDO_0015358

MESH ID

D015417

UMLS CUI

C0027888

MedGen ID

45066

SNOMED CT ID

398100001

General Information of Disease (ID: DISR0X2K)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 8 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
RAB7A	TTF6WAQ	Limited	Genetic Variation	[1]
GJB1	TTSJIRP	moderate	Genetic Variation	[2]
AMACR	TTLN1AP	Strong	Biomarker	[3]
LCAT	TTGZ91P	Strong	Altered Expression	[4]
RNMT	TTG45HY	Strong	Genetic Variation	[5]
SGCG	TTSMT9W	Strong	Genetic Variation	[6]
SLC12A6	TT8DFHE	Strong	Biomarker	[7]
TRPV4	TTKP2SU	Strong	Genetic Variation	[8]
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⏷ Show the Full List of 8 DTT(s)

This Disease Is Related to 2 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
HINT1	DEWJATF	Strong	Genetic Variation	[9]
HK1	DEDMAGE	Strong	Genetic Variation	[10]
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This Disease Is Related to 27 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ATP13A2	OTKWBUGK	Limited	Genetic Variation	[11]
DHTKD1	OTDQLSNT	Limited	Biomarker	[12]
FA2H	OT8HA13U	Limited	Genetic Variation	[11]
LRSAM1	OTOKWR6C	Limited	Biomarker	[13]
SBF2	OTBB8NO8	Limited	Biomarker	[14]
NDRG1	OTVO66BO	moderate	Biomarker	[15]
BICD2	OTVJ03NZ	Strong	Genetic Variation	[16]
COX6A1	OT77MV8G	Strong	Biomarker	[17]
DCAF8	OT3VFSLG	Strong	Genetic Variation	[18]
DNAJB2	OTZHPV5M	Strong	Genetic Variation	[19]
DYNC1H1	OTD1KRKO	Strong	Biomarker	[20]
FGD4	OTYXJQCW	Strong	Altered Expression	[21]
FIG4	OT501PY9	Strong	Biomarker	[22]
GARS1	OT5B6R9Y	Strong	Biomarker	[23]
GDAP1	OTQE1O25	Strong	Biomarker	[24]
KIF1B	OTI1XQTO	Strong	Genetic Variation	[25]
LMNA	OT3SG7ZR	Strong	Biomarker	[26]
MAD2L1BP	OT2O2IUJ	Strong	Genetic Variation	[25]
MFN2	OTPYN8A3	Strong	Genetic Variation	[27]
MTMR2	OTNCYGBP	Strong	Biomarker	[28]
NEFL	OTQESJV4	Strong	Biomarker	[29]
RFC1	OT3L5PK3	Strong	Biomarker	[30]
SACS	OTZGXQ8A	Strong	Genetic Variation	[31]
SH3TC2	OTJ6XY2A	Strong	Genetic Variation	[32]
SPTLC1	OTN0Z98K	Strong	Genetic Variation	[33]
TFG	OT2KJENI	Strong	Genetic Variation	[34]
EGR2	OTAVQ78J	Definitive	Biomarker	[35]
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⏷ Show the Full List of 27 DOT(s)

References

1	Charcot-Marie-Tooth disease (CMT): distinctive phenotypic and genotypic features in CMT type 2.J Neurol Sci. 2001 Feb 15;184(1):1-9. doi: 10.1016/s0022-510x(00)00497-4.
2	Three novel mutations in a group of Chinese patients with X-linked Charcot-Marie-Tooth disease.Clin Neurol Neurosurg. 2019 Sep;184:105430. doi: 10.1016/j.clineuro.2019.105430. Epub 2019 Jul 10.
3	Mutations in the gene encoding peroxisomal alpha-methylacyl-CoA racemase cause adult-onset sensory motor neuropathy. Nat Genet. 2000 Feb;24(2):188-91. doi: 10.1038/72861.
4	Lipid abnormalities in hereditary neuropathy. Part I. Serum non-polar lipids.J Neurol Sci. 1976 Oct;29(2-4):161-75. doi: 10.1016/0022-510x(76)90168-4.
5	Unilateral oculomotor palsy in Charcot-Marie-Tooth disease 1A (CMT 1A).Clin Neurol Neurosurg. 2017 Apr;155:20-21. doi: 10.1016/j.clineuro.2017.02.004. Epub 2017 Feb 13.
6	Carrier rates of four single-gene disorders in Croatian Bayash Roma.Genet Test Mol Biomarkers. 2014 Feb;18(2):83-7. doi: 10.1089/gtmb.2013.0323. Epub 2013 Nov 4.
7	Molecular insights into the normal operation, regulation, and multisystemic roles of K(+)-Cl(-) cotransporter 3 (KCC3).Am J Physiol Cell Physiol. 2017 Nov 1;313(5):C516-C532. doi: 10.1152/ajpcell.00106.2017. Epub 2017 Aug 16.
8	TRPV4-associated skeletal dysplasias. Am J Med Genet C Semin Med Genet. 2012 Aug 15;160C(3):190-204. doi: 10.1002/ajmg.c.31335. Epub 2012 Jul 12.
9	HINT1 gene pathogenic variants: the most common cause of recessive hereditary motor and sensory neuropathies in Russian patients.Mol Biol Rep. 2020 Feb;47(2):1331-1337. doi: 10.1007/s11033-019-05238-z. Epub 2019 Dec 17.
10	HSMNR belongs to the most frequent types of hereditary neuropathy in the Czech Republic and is twice more frequent than HMSNL.Clin Genet. 2016 Aug;90(2):161-5. doi: 10.1111/cge.12745. Epub 2016 Mar 4.
11	Genetic and phenotypic characterization of complex hereditary spastic paraplegia.Brain. 2016 Jul;139(Pt 7):1904-18. doi: 10.1093/brain/aww111. Epub 2016 May 23.
12	DHTKD1 Deficiency Causes Charcot-Marie-Tooth Disease in Mice.Mol Cell Biol. 2018 Jun 14;38(13):e00085-18. doi: 10.1128/MCB.00085-18. Print 2018 Jul 1.
13	Loss of the E3 ubiquitin ligase LRSAM1 sensitizes peripheral axons to degeneration in a mouse model of Charcot-Marie-Tooth disease.Dis Model Mech. 2013 May;6(3):780-92. doi: 10.1242/dmm.010942. Epub 2013 Mar 8.
14	Loss of the inactive myotubularin-related phosphatase Mtmr13 leads to a Charcot-Marie-Tooth 4B2-like peripheral neuropathy in mice.Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4916-21. doi: 10.1073/pnas.0800742105. Epub 2008 Mar 18.
15	HMSN Lom in 12 Czech patients, with one unusual case due to uniparental isodisomy of chromosome 8.J Hum Genet. 2017 Mar;62(3):431-435. doi: 10.1038/jhg.2016.148. Epub 2016 Dec 22.
16	BICD2 mutational analysis in hereditary spastic paraplegia and hereditary motor and sensory neuropathy.Muscle Nerve. 2019 Apr;59(4):484-486. doi: 10.1002/mus.26394. Epub 2018 Dec 21.
17	A mutation of COX6A1 causes a recessive axonal or mixed form of Charcot-Marie-Tooth disease. Am J Hum Genet. 2014 Sep 4;95(3):294-300. doi: 10.1016/j.ajhg.2014.07.013. Epub 2014 Aug 21.
18	Ubiquitin ligase defect by DCAF8 mutation causes HMSN2 with giant axons. Neurology. 2014 Mar 11;82(10):873-8. doi: 10.1212/WNL.0000000000000206. Epub 2014 Feb 5.
19	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.
20	A novel mouse model carrying a human cytoplasmic dynein mutation shows motor behavior deficits consistent with Charcot-Marie-Tooth type 2O disease.Sci Rep. 2018 Jan 29;8(1):1739. doi: 10.1038/s41598-018-20081-1.
21	Expression of FGD4 positively correlates with the aggressive phenotype of prostate cancer.BMC Cancer. 2018 Dec 17;18(1):1257. doi: 10.1186/s12885-018-5096-9.
22	Neuronal expression of Fig4 is both necessary and sufficient to prevent spongiform neurodegeneration.Hum Mol Genet. 2012 Aug 15;21(16):3525-34. doi: 10.1093/hmg/dds179. Epub 2012 May 11.
23	Charcot-Marie-Tooth-linked mutant GARS is toxic to peripheral neurons independent of wild-type GARS levels.PLoS Genet. 2011 Dec;7(12):e1002399. doi: 10.1371/journal.pgen.1002399. Epub 2011 Dec 1.
24	Lack of GDAP1 induces neuronal calcium and mitochondrial defects in a knockout mouse model of charcot-marie-tooth neuropathy.PLoS Genet. 2015 Apr 10;11(4):e1005115. doi: 10.1371/journal.pgen.1005115. eCollection 2015 Apr.
25	Severe demyelinating hypertrophic polyneuropathy caused by a de novo frameshift mutation within the intracellular domain of myelin protein zero (MPZ/P0).J Neurol Sci. 2009 Jun 15;281(1-2):113-5. doi: 10.1016/j.jns.2009.03.008. Epub 2009 Apr 3.
26	Homozygous defects in LMNA, encoding lamin A/C nuclear-envelope proteins, cause autosomal recessive axonal neuropathy in human (Charcot-Marie-Tooth disorder type 2) and mouse. Am J Hum Genet. 2002 Mar;70(3):726-36. doi: 10.1086/339274. Epub 2002 Jan 17.
27	Genotype-phenotype correlations in Charcot-Marie-Tooth disease type 2 caused by mitofusin 2 mutations.Arch Neurol. 2009 Dec;66(12):1511-6. doi: 10.1001/archneurol.2009.284.
28	An animal model for Charcot-Marie-Tooth disease type 4B1.Hum Mol Genet. 2005 Dec 1;14(23):3685-95. doi: 10.1093/hmg/ddi400. Epub 2005 Oct 25.
29	Neurofilament light polypeptide gene N98S mutation in mice leads to neurofilament network abnormalities and a Charcot-Marie-Tooth Type 2E phenotype.Hum Mol Genet. 2015 Apr 15;24(8):2163-74. doi: 10.1093/hmg/ddu736. Epub 2014 Dec 30.
30	Biallelic expansion of an intronic repeat in RFC1 is a common cause of late-onset ataxia. Nat Genet. 2019 Apr;51(4):649-658. doi: 10.1038/s41588-019-0372-4. Epub 2019 Mar 29.
31	SACS variants are a relevant cause of autosomal recessive hereditary motor and sensory neuropathy.Hum Genet. 2018 Dec;137(11-12):911-919. doi: 10.1007/s00439-018-1952-6. Epub 2018 Nov 21.
32	Genetics of the Charcot-Marie-Tooth disease in the Spanish Gypsy population: the hereditary motor and sensory neuropathy-Russe in depth.Clin Genet. 2013 Jun;83(6):565-70. doi: 10.1111/cge.12015. Epub 2012 Oct 10.
33	Targeted high-throughput sequencing identifies mutations in atlastin-1 as a cause of hereditary sensory neuropathy type I. Am J Hum Genet. 2011 Jan 7;88(1):99-105. doi: 10.1016/j.ajhg.2010.12.003. Epub 2010 Dec 30.
34	Muscle pathology of hereditary motor and sensory neuropathy with proximal dominant involvement with TFG mutation.Muscle Nerve. 2019 Dec;60(6):739-744. doi: 10.1002/mus.26683. Epub 2019 Aug 30.
35	Congenital hypomyelinating neuropathy with lethal conduction failure in mice carrying the Egr2 I268N mutation.J Neurosci. 2009 Feb 25;29(8):2312-21. doi: 10.1523/JNEUROSCI.2168-08.2009.