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

Justine Lerat, Corinne Magdelaine, Anne‐Françoise Roux, Léa Darnaud, Hélène Beauvais‐Dzugan, Steven Naud, Laurence Richard, Paco Derouault, Karima Ghorab, Laurent Magy, Jean‐Michel Vallat, Pascal Cintas, Eric Bieth, Marie‐Christine Arne‐Bes, Cyril Goizet, Caroline Espil‐Taris, Hubert Journel, Annick Toutain, Jon Andoni Urtizberea, Odile Boespflug‐Tanguy, Fanny Laffargue, Philippe Corcia, Laurent Pasquier, Mélanie Fradin, Sylva Napuri, Jonathan Ciron, Jean‐Marc Boulesteix, Franck Sturtz, Anne‐Sophie Lia
Mol Genet Genomic Med. 2019-08-08; 7(9):
DOI: 10.1002/mgg3.839

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1. Mol Genet Genomic Med. 2019 Sep;7(9):e839. doi: 10.1002/mgg3.839. Epub 2019 Aug

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

Lerat J(1)(2), Magdelaine C(1)(3), Roux AF(4)(5), Darnaud L(3), Beauvais-Dzugan
H(1)(3), Naud S(3), Richard L(6), Derouault P(3), Ghorab K(1)(6), Magy L(1)(6),
Vallat JM(6), Cintas P(7)(8), Bieth E(9), Arne-Bes MC(7), Goizet C(10),
Espil-Taris C(11), Journel H(12), Toutain A(13), Urtizberea JA(14),
Boespflug-Tanguy O(15), Laffargue F(16), Corcia P(17), Pasquier L(18), Fradin
M(18), Napuri S(19), Ciron J(20), Boulesteix JM(21), Sturtz F(1)(3), Lia

Author information:
(1)University of Limoges, MMNP, Limoges, France.
(2)Service Oto-Rhino-Laryngologie et Chirurgie Cervico-Faciale, CHU Limoges,
Limoges, France.
(3)Service Biochimie et Génétique Moléculaire, CHU Limoges, Limoges, France.
(4)Laboratoire de Génétique Moléculaire, CHU Montpellier, Montpellier, France.
(5)University of Montpellier, Montpellier, France.
(6)CRMR Neuropathies Périphériques Rares, CHU Limoges, Limoges, France.
(7)Service de Neurologie et d’explorations fonctionnelles, CHU Toulouse,
Toulouse, France.
(8)Service de Neurologie, Centre de référence de pathologie neuromusculaire, CHU
Toulouse, Toulouse, France.
(9)Service de Génétique Médicale, CHU Toulouse, Toulouse, France.
(10)Service de Neurogénétique, CHU Bordeaux, Bordeaux, France.
(11)Service de Génétique médicale, CHU Bordeaux, Bordeaux, France.
(12)Service de Génétique Médicale, CH Bretagne Atlantique, Vannes, France.
(13)Service de Génétique, CHU Tours, Tours, France.
(14)Centre de référence Neuromusculaire, Hôpital marin, Hendaye, France.
(15)Service de Neurogénétique, Hôpital Robert-Debré AP-HP, Paris, France.
(16)Service de Génétique médicale, CHU Clermont-Ferrand, Clermont-Ferrand,
(17)Service de Neurologie, CHU Tours, Tours, France.
(18)Service de Génétique médicale, CHU Rennes, Rennes, France.
(19)Service de Pédiatrie, CHU Rennes, Rennes, France.
(20)Service de Neurologie, CHU Poitiers, Poitiers, France.
(21)Service Neurologie, CHU Cahors, Cahors, France.

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
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.

© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley
Periodicals, Inc.

DOI: 10.1002/mgg3.839
PMCID: PMC6732311
PMID: 31393079 [Indexed for MEDLINE]

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