Objectives: Mutations in DFNA5 may lead to autosomal dominant non-syndromic sensorineural hearing loss (NSHL). To date, only four DFNA5 mutations have been reported, all resulting in skipping of exon 8 at the mRNA level. In this study, we aim to characterize the clinical features and the genetic cause of a Chinese DFNA5 family.
Methods: Targeted next-generation sequencing of 79 known deafness genes was performed in the proband. Co-segregation between the disease phenotype and the potentially pathogenic variant was confirmed in all family members by Sanger sequencing.
Results: A novel heterozygous c.991-2A>G mutation in DFNA5 was identified in this family segregating with the autosomal dominant, late-onset NSHL. This mutation was located in the conventional splice site in intron 7 and was likely to result in skipping of exon 8. The severity of hearing impairment varied intrafamilially.
Conclusion: We identified a novel c.991-2A>G mutation in DFNA5 which again may lead to exon 8 skipping at the mRNA level. Our findings supported that the DFNA5-associated NSHL results from a specific gain-of-function mechanism.
Keywords: Autosomal dominant hearing loss; DFNA5; Spice site mutation; Target next-generation sequencing.
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