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Genetic etiology of non-syndromic hearing loss in Europe

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Abstract

Hearing impairment not etiologically associated with clinical signs in other organs (non-syndromic) is genetically heterogeneous, so that over 120 genes are currently known to be involved. The frequency of mutations in each gene and the most frequent mutations vary throughout populations. Here we review the genetic etiology of non-syndromic hearing impairment (NSHI) in Europe. Over the years, epidemiological data were scarce because of the large number of involved genes, whose screening was not cost-effective until implementation of massively parallel DNA sequencing. In Europe, the most common form of autosomal recessive NSHI is DFNB1, which accounts for 11–57% of the cases. Mutations in STRC account for 16% of the recessive cases, and only a few more (MYO15A, MYO7A, LOXHD1, USH2A, TMPRSS3, CDH23, TMC1, OTOF, OTOA, SLC26A4, ADGRV1 and TECTA) have contributions higher than 2%. As regards autosomal-dominant NSHI, DFNA22 (MYO6) and DFNA8/12 (TECTA) represent the most common forms, accounting for 21% and 18% of elucidated cases, respectively. The contribution of ACTG1 and WFS1 drops to 9% in both cases, followed by POU4F3 (6.5%), MYO7A (5%), MYH14 and COL11A2 (4% each). Four additional genes contribute 2.5% each one (MITF, KCNQ4, EYA4, SOX10) and the remaining are residually represented. X-linked hearing loss and maternally-inherited NSHI have minor contributions in most countries. Further knowledge on the genetic epidemiology of NSHI in Europe needs a standardization of the experimental approaches and a stratification of the results according to clinical features, familial history and patterns of inheritance, to facilitate comparison between studies.

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Funding

Research on the genetics of hearing impairment in the laboratory of the authors has received funding from Instituto de Salud Carlos III cofounded with the European Regional Development Fund (ERDF), “A way to make Europe”) within the National Plans for Scientific and Technical Research and Innovation 2013–2016, 2017–2020 and 2021–2024 (PI17/00572 and PI20/00619 to IdC; PI17/1659; PI20/0429 and IMP/00009 to MAM-P); from the Regional Government of Madrid (CAM, B2017/BMD3721 to MAM-P).

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  1. Servicio de Genética, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain

    Ignacio del Castillo, Matías Morín, María Domínguez-Ruiz & Miguel A. Moreno-Pelayo

  2. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain

    Ignacio del Castillo, Matías Morín, María Domínguez-Ruiz & Miguel A. Moreno-Pelayo

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  1. Ignacio del Castillo
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  4. Miguel A. Moreno-Pelayo
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All authors conceived the study, wrote the text and prepared Tables and Figures.

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del Castillo, I., Morín, M., Domínguez-Ruiz, M. et al. Genetic etiology of non-syndromic hearing loss in Europe. Hum Genet 141, 683–696 (2022). https://doi.org/10.1007/s00439-021-02425-6

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