Hearing loss in inherited peripheral neuropathies: Molecular diagnosis by NGS in a French series.
Adult
Age of Onset
Aged
Aged, 80 and over
Alleles
Computational Biology
Female
France
/ epidemiology
Genetic Association Studies
/ methods
Genetic Predisposition to Disease
Genetic Testing
Genotype
Hearing Loss
/ diagnosis
High-Throughput Nucleotide Sequencing
Humans
Inheritance Patterns
Male
Middle Aged
Mutation
Pedigree
Peripheral Nervous System Diseases
/ diagnosis
Phenotype
Charcot-Marie-Tooth
NGS
hearing loss
neuropathy
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
29
01
2019
revised:
19
05
2019
accepted:
22
05
2019
pubmed:
9
8
2019
medline:
20
6
2020
entrez:
9
8
2019
Statut:
ppublish
Résumé
The most common inherited peripheral neuropathy is Charcot-Marie-Tooth disease (CMT), with a prevalence of 1/2500. Other symptoms can be associated to the condition, such as hearing loss. Currently, no global hearing impairment assessment has been determined, and the physiopathology is not well known. The aim of the study was to analyze among a French series of 3,412 patients with inherited peripheral neuropathy (IPN), the ones who also suffer from hearing loss, to establish phenotype-genotype correlations. An NGS strategy for IPN one side and nonsyndromic hearing loss (NSHL) on the other side, were performed. Hearing loss (HL) was present in only 44 patients (1.30%). The clinical data of 27 patients were usable. Demyelinating neuropathy was diagnosed in 15 cases and axonal neuropathy in 12 cases. HL varied from mild to profound. Five cases of auditory neuropathy were noticed. Diagnosis was made for 60% of these patients. Seven novel pathogenic variants were discovered in five different genes: PRPS1; MPZ; SH3TC2; NEFL; and ABHD12. Two patients with PMP22 variant, had also an additional variant in COCH and MYH14 respectively. No pathogenic variant was found at the DFNB1 locus. Genotype-phenotype correlations do exist, especially with SH3TC2, PRPS1, ABHD12, NEFL, and TRPV4. Involvement of PMP22 is not enough to explain hearing loss in patients suffering from IPN. HL can be due to cochlear impairment and/or auditory nerve dysfunction. HL is certainly underdiagnosed, and should be evaluated in every patient suffering from IPN.
Sections du résumé
BACKGROUND
The most common inherited peripheral neuropathy is Charcot-Marie-Tooth disease (CMT), with a prevalence of 1/2500. Other symptoms can be associated to the condition, such as hearing loss. Currently, no global hearing impairment assessment has been determined, and the physiopathology is not well known.
METHODS
The aim of the study was to analyze among a French series of 3,412 patients with inherited peripheral neuropathy (IPN), the ones who also suffer from hearing loss, to establish phenotype-genotype correlations. An NGS strategy for IPN one side and nonsyndromic hearing loss (NSHL) on the other side, were performed.
RESULTS
Hearing loss (HL) was present in only 44 patients (1.30%). The clinical data of 27 patients were usable. Demyelinating neuropathy was diagnosed in 15 cases and axonal neuropathy in 12 cases. HL varied from mild to profound. Five cases of auditory neuropathy were noticed. Diagnosis was made for 60% of these patients. Seven novel pathogenic variants were discovered in five different genes: PRPS1; MPZ; SH3TC2; NEFL; and ABHD12. Two patients with PMP22 variant, had also an additional variant in COCH and MYH14 respectively. No pathogenic variant was found at the DFNB1 locus. Genotype-phenotype correlations do exist, especially with SH3TC2, PRPS1, ABHD12, NEFL, and TRPV4.
CONCLUSION
Involvement of PMP22 is not enough to explain hearing loss in patients suffering from IPN. HL can be due to cochlear impairment and/or auditory nerve dysfunction. HL is certainly underdiagnosed, and should be evaluated in every patient suffering from IPN.
Identifiants
pubmed: 31393079
doi: 10.1002/mgg3.839
pmc: PMC6732311
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e839Informations de copyright
© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
Références
Hum Mutat. 2016 Dec;37(12):1354-1362
pubmed: 27650058
Hum Mol Genet. 1996 Jul;5(7):1047-50
pubmed: 8817345
J Peripher Nerv Syst. 2016 Sep;21(3):142-9
pubmed: 27231023
Brain. 2007 Feb;130(Pt 2):394-403
pubmed: 17052987
Mol Genet Genomic Med. 2019 Sep;7(9):e839
pubmed: 31393079
J Neurol Neurosurg Psychiatry. 2017 Jul;88(7):575-585
pubmed: 28501821
Hum Mutat. 2011 Jun;32(6):669-77
pubmed: 21480433
J Med Genet. 2015 Oct;52(10):681-90
pubmed: 26246519
Eur J Hum Genet. 2002 Feb;10(2):95-9
pubmed: 11938438
Case Rep Med. 2018 Mar 26;2018:1760978
pubmed: 29780422
Brain Dev. 2019 Feb;41(2):201-204
pubmed: 30177296
J Laryngol Otol. 2006 Jun;120(6):508-10
pubmed: 16772060
J Hum Genet. 2009 Feb;54(2):94-7
pubmed: 19158810
Cochlear Implants Int. 2012 Aug;13(3):184-7
pubmed: 22333975
Otol Neurotol. 2005 May;26(3):405-14
pubmed: 15891642
PLoS One. 2018 Jan 2;13(1):e0188578
pubmed: 29293505
Neurol Sci. 2013 Sep;34(9):1705-7
pubmed: 23263778
Ann Neurol. 1994 May;35(5):608-15
pubmed: 8179305
Clin Genet. 2007 Apr;71(4):343-9
pubmed: 17470135
Hum Mol Genet. 1995 Jun;4(6):1073-6
pubmed: 7655461
Am J Med Genet. 2002 Apr 1;108(4):295-303
pubmed: 11920834
Ann Otol Rhinol Laryngol. 2007 May;116(5):349-57
pubmed: 17561763
J Peripher Nerv Syst. 2012 Mar;17(1):112-22
pubmed: 22462672
Sci Rep. 2017 Dec 1;7(1):16783
pubmed: 29196752
Neurology. 2013 Oct 29;81(18):1617-25
pubmed: 24078732
Neurology. 2012 Jul 10;79(2):192-4
pubmed: 22675077
Hum Mutat. 2014 Dec;35(12):1506-1513
pubmed: 25230692
Nat Genet. 2004 May;36(5):449-51
pubmed: 15064763
Nat Genet. 1992 Jun;1(3):171-5
pubmed: 1303230