Ultrarare heterozygous pathogenic variants of genes causing dominant forms of early-onset deafness underlie severe presbycusis

• DOI: 10.1073/pnas.2010782117
• Publication Date: 2020-11-24T02:42:10Z
• Authors: Sophie Boucher; Fabienne Wong Jun...; Sedigheh Delmaghani; Andrea Lelli; Amrit Singh-Estiv...; Typhaine Dupont; Magali Niasme-Grare; Vincent Michel; Nicolas Wolff; Amel Bahloul; Yosra Bouyacoub; Didier Bouccara; Bernard Fraysse; Olivier Deguine; Lionel Collet; Hung Thai-Van; Eugen Ionescu; Jean-Louis Kemeny; Fabrice Giraudet; Jean-Pierre Lavie...; Arnaud Devèze; Anne-Laure Roudev...; Christophe Vincent; Christian Renard; Valérie Franco-Vidal; Claire Thibult-Apt; Vincent Darrouzet; Eric Bizaguet; Arnaud Coez; Hugues Aschard; Nicolas Michalski; Gaëlle M. Lefevre; Anne Aubois; Paul Avan; Crystel Bonnet; Christine Petit
• Keywords: Presbycusis

Significance Presbycusis, or age-related hearing loss, is a major public health issue and the principal potentially modifiable risk factor for dementia. It caused by environmental factors largely uncharacterized genetic factors. We compared DNA sequences across genomic coding regions between familial sporadic cases of severe presbycusis controls with normal hearing. The frequency ultrarare predicted pathogenic variants in genes known to cause dominant early-onset forms deafness was significantly higher both than controls. Pathogenicity many these established complementary analyses. Ultrarare have large effect size are monogenic disorders. These findings open up possibilities curing gene therapy.