Human genomics · 2025
A multicenter study reveals a novel pathogenic splice-site founder variant in OTOF.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Brownstein Zippora, Kamal Lara, Mishan-Montefiori Shir, Hoffman Yael, Fine Dina, Hirsch Yoel, Weiden Tzvi, Birnbaum Rivka, Mor-Shaked Hagar, Davidov Bella, Yaron Yuval, Avraham Karen B
Аннотация
BACKGROUND: Over 200 pathogenic variants in the OTOF gene encoding otoferlin are associated with sensorineural hearing loss (SNHL) and auditory neuropathy spectrum disorders (ANSD). RESULTS: A novel splice variant, OTOF c.898-18G > A, was detected in seven Jewish Moroccan families with both SNHL and ANSD in an Israeli multicenter study. The effect on splicing was confirmed by a minigene assay, which demonstrated skipping of exon 10. This variant is absent in gnomAD and in all Jewish ethnic groups except for Moroccan Jews, with a carrier rate of 1.5% in this ancestry, suggesting a founder effect. CONCLUSIONS: The OTOF variant represents a second founder allele associated with hearing loss in the Moroccan Jewish community and may serve as a candidate for gene therapy.