| Autor: |
Suzanne E, de Bruijn, Jeroen J, Smits, Chang, Liu, Cornelis P, Lanting, Andy J, Beynon, Joëlle, Blankevoort, Jaap, Oostrik, Wouter, Koole, Erik, de Vrieze, Cor W R J, Cremers, Frans P M, Cremers, Susanne, Roosing, Helger G, Yntema, Henricus P M, Kunst, Bo, Zhao, Ronald J E, Pennings, Hannie, Kremer, J M, van de Kamp |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
J Med Genet |
| ISSN: |
1468-6244 |
| Popis: |
BACKGROUND: Hearing loss is one of the most prevalent disabilities worldwide, and has a significant impact on quality of life. The adult-onset type of the condition is highly heritable but the genetic causes are largely unknown, which is in contrast to childhood-onset hearing loss. METHODS: Family and cohort studies included exome sequencing and characterisation of the hearing phenotype. Ex vivo protein expression addressed the functional effect of a DNA variant. RESULTS: An in-frame deletion of 12 nucleotides in RIPOR2 was identified as a highly penetrant cause of adult-onset progressive hearing loss that segregated as an autosomal dominant trait in 12 families from the Netherlands. Hearing loss associated with the deletion in 63 subjects displayed variable audiometric characteristics and an average (SD) age of onset of 30.6 (14.9) years (range 0–70 years). A functional effect of the RIPOR2 variant was demonstrated by aberrant localisation of the mutant RIPOR2 in the stereocilia of cochlear hair cells and failure to rescue morphological defects in RIPOR2-deficient hair cells, in contrast to the wild-type protein. Strikingly, the RIPOR2 variant is present in 18 of 22 952 individuals not selected for hearing loss in the Southeast Netherlands. CONCLUSION: Collectively, the presented data demonstrate that an inherited form of adult-onset hearing loss is relatively common, with potentially thousands of individuals at risk in the Netherlands and beyond, which makes it an attractive target for developing a (genetic) therapy. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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