Analysis of Rotterdam Study cohorts confirms a previously identified RIPOR2 in-frame deletion as a prevalent genetic factor in phenotypically variable adult-onset hearing loss (DFNA21) in the Netherlands.

Autor:	Velde HM; Department of Otorhinolaryngology, Radboudumc, Nijmegen, The Netherlands.; Donders Institute for Brain Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands., Homans NC; Department of Otorhinolaryngology Head and Neck Surgery, Erasmus Medical Center, Rotterdam, The Netherlands., Goedegebure A; Department of Otorhinolaryngology Head and Neck Surgery, Erasmus Medical Center, Rotterdam, The Netherlands., Lanting CP; Department of Otorhinolaryngology, Radboudumc, Nijmegen, The Netherlands.; Donders Institute for Brain Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands., Pennings RJE; Department of Otorhinolaryngology, Radboudumc, Nijmegen, The Netherlands.; Donders Institute for Brain Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands., Kremer H; Donders Institute for Brain Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands Hannie.Kremer@radboudumc.nl.; Department of Otorhinolaryngology and Department of Human Genetics, Radboudumc, Nijmegen, The Netherlands.
Jazyk:	angličtina
Zdroj:	Journal of medical genetics [J Med Genet] 2023 Nov; Vol. 60 (11), pp. 1061-1066. Date of Electronic Publication: 2023 May 10.
DOI:	10.1136/jmg-2023-109146
Abstrakt:	Background: A 12-nucleotide RIPOR2 in-frame deletion was recently identified as a relatively common and highly penetrant cause of autosomal dominant non-syndromic sensorineural hearing loss, type DFNA21, in the Netherlands. The associated hearing phenotype is variable. The allele frequency (AF) of 0.039% of this variant was determined in a local cohort, and the reported phenotype may be biased because studied families were identified based on index patients with hearing loss (HL). In this study, we determine the AF in a cohort from a different geographical region of the Netherlands. Additionally, we examine the hearing phenotype in individuals with the variant but not selected for HL. Methods: The AF was determined in participants of the Rotterdam Study (RS), a large cohort study. The phenotype was characterised using individual clinical hearing data, including audiograms. Results: The observed AF in the RS cohort was 0.072% and not statistically significantly different from the previously observed 0.039%. The AF in the two cohorts combined was 0.052%. Consistent with previous findings, we found a highly variable audiometric phenotype with non-penetrance of HL in 40% of subjects aged 55-81, which is higher than the 10% at age 50 previously observed. Conclusion: We found an overall higher AF and lower penetrance than previously reported, confirming that DFNA21 is relatively common in the Netherlands. This supports its potential suitability as a target for therapeutic development. Studying possible modifying factors is essential to explain the phenotypical variability and to identify patients eligible for such a therapy. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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