Hearing loss in inherited peripheral neuropathies: Molecular diagnosis by NGS in a French series

被引：16

作者：

Lerat, Justine ^{[1
,2
]}

MagdelaineU, Corinne ^{[1
,3
]}

Roux, Anne-Francoise ^{[4
,5
]}

Darnaud, Lea ^{[3
]}

Beauvais-Dzugan, Helene ^{[1
,3
]}

Naud, Steven ^{[3
]}

Richard, Laurence ^{[6
]}

Derouault, Paco ^{[3
]}

Ghorab, Karima ^{[1
,6
]}

Magy, Laurent ^{[1
,6
]}

Vallat, Jean-Michel ^{[6
]}

Cintas, Pascal ^{[7
,8
]}

Bieth, Eric ^{[9
]}

Arne-Bes, Marie-Christine ^{[7
]}

Goizet, Cyril ^{[10
]}

Espil-Taris, Caroline ^{[11
]}

Journel, Hubert ^{[12
]}

Toutain, Annick ^{[13
]}

Urtizberea, Jon Andoni ^{[14
]}

Boespflug-Tanguy, Odile ^{[15
]}

Laffargue, Fanny ^{[16
]}

Corcia, Philippe ^{[17
]}

Pasquier, Laurent ^{[18
]}

Fradin, Melanie ^{[18
]}

Napuri, Sylva ^{[19
]}

Ciron, Jonathan ^{[20
]}

Boulesteix, Jean-Marc ^{[21
]}

Sturtz, Franck ^{[1
,3
]}

Lia, Anne-Sophie ^{[1
,3
]}

机构：

[1] Univ Limoges, MMNP, Limoges, France

[2] CHU Limoges, Serv Otorhinolaryngol & Chirurg Cerv Faciale, Limoges, France

[3] CHU Limoges, Serv Biochim & Genet Mol, Limoges, France

[4] CHU Montpellier, Lab Genet Mol, Montpellier, France

[5] Univ Montpellier, Montpellier, France

[6] CHU Limoges, CRMR Neuropathies Peripher Rares, Limoges, France

[7] CHU Toulouse, Serv Neurol & Explorat Fonct, Toulouse, France

[8] CHU Toulouse, Ctr Reference Pathol Neuromusculaire, Serv Neurol, Toulouse, France

[9] CHU Toulouse, Serv Genet Med, Toulouse, France

[10] CHU Bordeaux, Serv Neurogenet, Bordeaux, France

[11] CHU Bordeaux, Serv Genet Med, Bordeaux, France

[12] CH Bretagne Atlantique, Serv Genet Med, Vannes, France

[13] CHU Tours, Serv Genet, Tours, France

[14] Hop Marin, Ctr Reference Neuromusculaire, Hendaye, France

[15] Hop Robert Debre, AP HP, Serv Neurogenet, Paris, France

[16] CHU Clermont Ferrand, Serv Genet Med, Clermont Ferrand, France

[17] CHU Tours, Serv Neurol, Tours, France

[18] CHU Rennes, Serv Genet Med, Rennes, France

[19] CHU Rennes, Serv Pediat, Rennes, France

[20] CHU Poitiers, Serv Neurol, Poitiers, France

[21] CHU Cahors, Serv Neurol, Cahors, France

来源：

MOLECULAR GENETICS & GENOMIC MEDICINE | 2019年 / 7卷 / 09期

关键词：

Charcot-Marie-Tooth; hearing loss; neuropathy; NGS; HEREDITARY MOTOR; GENE-MUTATIONS; SH3TC2; GENE; DEAFNESS; PHENOTYPE; IMPAIRMENT; FAMILY;

D O I：

10.1002/mgg3.839

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页数：12

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