Ultrarare heterozygous pathogenic variants of genes causing dominant forms of early-onset deafness underlie severe presbycusis
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- Sophie Boucher
- Institut de l’Audition, Institut Pasteur, INSERM, 75012 Paris, France;
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- Fabienne Wong Jun Tai
- Institut de l’Audition, Institut Pasteur, INSERM, 75012 Paris, France;
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- Sedigheh Delmaghani
- Institut de l’Audition, Institut Pasteur, INSERM, 75012 Paris, France;
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- Andrea Lelli
- Institut de l’Audition, Institut Pasteur, INSERM, 75012 Paris, France;
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- Amrit Singh-Estivalet
- Institut de l’Audition, Institut Pasteur, INSERM, 75012 Paris, France;
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- Typhaine Dupont
- Institut de l’Audition, Institut Pasteur, INSERM, 75012 Paris, France;
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- Magali Niasme-Grare
- Institut de l’Audition, Institut Pasteur, INSERM, 75012 Paris, France;
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- Vincent Michel
- Institut de l’Audition, Institut Pasteur, INSERM, 75012 Paris, France;
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- Nicolas Wolff
- Unité Récepteurs-Canaux, Institut Pasteur, 75015 Paris, France;
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- Amel Bahloul
- Institut de l’Audition, Institut Pasteur, INSERM, 75012 Paris, France;
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- Yosra Bouyacoub
- Institut de l’Audition, Institut Pasteur, INSERM, 75012 Paris, France;
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- Didier Bouccara
- Hôpital Beaujon, Hôpitaux Universitaires Paris Nord val-de-Seine, AP-HP, 92110 Clichy, France;
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- Bernard Fraysse
- Centre Hospitalier Universitaire, Service d’Oto-Rhino-Laryngologie et Chirurgie Cervico-Faciale, Hôpital Larrey, 31400 Toulouse, France;
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- Olivier Deguine
- Centre Hospitalier Universitaire, Service d’Oto-Rhino-Laryngologie et Chirurgie Cervico-Faciale, Hôpital Larrey, 31400 Toulouse, France;
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- Lionel Collet
- Centre Hospitalier Universitaire, Audiologie et Explorations Orofaciales, Hôpital Lyon-Sud, 69495 Lyon, France;
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- Hung Thai-Van
- Institut de l’Audition, Institut Pasteur, INSERM, 75012 Paris, France;
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- Eugen Ionescu
- Centre Hospitalier Universitaire, Exploration Fonctionnelle Audiologie et Vestibulaire, Hôpital Edouard Herriot, 69437 Lyon, France;
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- Jean-Louis Kemeny
- Centre Hospitalier Universitaire, Service d’Anatomo-Pathologie, Hôpital Gabriel Montpied, 63000 Clermont-Ferrand, France;
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- Fabrice Giraudet
- Unité Mixte de Recherche (UMR) 1107, INSERM, 63001 Clermont-Ferrand, France;
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- Jean-Pierre Lavieille
- Centre Hospitalier Universitaire, Service d’Oto-Rhino-Laryngologie, Hôpital Nord, 13015 Marseille, France;
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- Arnaud Devèze
- Centre Hospitalier Universitaire, Service d’Oto-Rhino-Laryngologie, Hôpital Nord, 13015 Marseille, France;
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- Anne-Laure Roudevitch-Pujol
- Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts, Centre d’Investigation Clinique, 75012 Paris, France;
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- Christophe Vincent
- Centre Hospitalier Universitaire, Service d’Otologie et Otoneurologie, Hôpital Roger Salengro, 59000 Lille, France;
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- Christian Renard
- Laboratoire d’Audiologie Renard, 59000 Lille, France;
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- Valérie Franco-Vidal
- Centre Hospitalier Universitaire, Service d’Oto-Rhino-Laryngologie et Chirurgie Cervico-Faciale, Hôpital Pellegrin, 33076 Bordeaux, France;
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- Claire Thibult-Apt
- Centre Hospitalier Universitaire, Service d’Oto-Rhino-Laryngologie et Chirurgie Cervico-Faciale, Hôpital Pellegrin, 33076 Bordeaux, France;
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- Vincent Darrouzet
- Centre Hospitalier Universitaire, Service d’Oto-Rhino-Laryngologie et Chirurgie Cervico-Faciale, Hôpital Pellegrin, 33076 Bordeaux, France;
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- Eric Bizaguet
- Laboratoire de Correction Auditive, Eric Bizaguet, 75001 Paris, France;
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- Arnaud Coez
- Laboratoire de Correction Auditive, Eric Bizaguet, 75001 Paris, France;
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- Hugues Aschard
- Centre de Bioinformatique, Biostatistique et Biologie Intégrative, Institut Pasteur, 75015 Paris, France;
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- Nicolas Michalski
- Institut de l’Audition, Institut Pasteur, INSERM, 75012 Paris, France;
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- Gaëlle M. Lefevre
- Institut de l’Audition, Institut Pasteur, INSERM, 75012 Paris, France;
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- Anne Aubois
- Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts, Centre d’Investigation Clinique, 75012 Paris, France;
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- Paul Avan
- Institut de l’Audition, Institut Pasteur, INSERM, 75012 Paris, France;
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- Crystel Bonnet
- Institut de l’Audition, Institut Pasteur, INSERM, 75012 Paris, France;
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- Christine Petit
- Institut de l’Audition, Institut Pasteur, INSERM, 75012 Paris, France;
書誌事項
- 公開日
- 2020-11-23
- 権利情報
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- https://www.pnas.org/site/aboutpnas/licenses.xhtml
- DOI
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- 10.1073/pnas.2010782117
- 公開者
- Proceedings of the National Academy of Sciences
この論文をさがす
説明
<jats:title>Significance</jats:title> <jats:p>Presbycusis, or age-related hearing loss, is a major public health issue and the principal potentially modifiable risk factor for dementia. It is caused by environmental factors and largely uncharacterized genetic factors. We compared DNA sequences across genomic coding regions between familial or sporadic cases of severe presbycusis and controls with normal hearing. The frequency of ultrarare predicted pathogenic variants in genes known to cause dominant early-onset forms of deafness was significantly higher in both familial and sporadic cases than in controls. Pathogenicity of many of these variants was established with complementary analyses. Ultrarare variants have a large effect size and are known to cause monogenic disorders. These findings open up possibilities for curing these forms of presbycusis by gene therapy.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 117 (49), 31278-31289, 2020-11-23
Proceedings of the National Academy of Sciences
