Intronic mutation causes an atypical splicing defect resulting in auditory neuropathy spectrum disorder.

Pathogenic variants in cause auditory neuropathy spectrum disorder (ANSD), namely prelingual nonsyndromic ANSD and temperature-sensitive ANSD (TS-ANSD). All study subjects provided blood sample for genetic analysis and sequencing. Wholeexome sequencing was carried out to identify the causative pathogenic variant. RNAwas extracted to analyse the messenger RNA (mRNA) resulting from the transcription of OTOF. Here, we identified a family with OTOF-related ANSD. This disorder was caused by an intronic mutation in (NM_194248: c.2406>4A[G). In further analysis, we proved that this variant causes a splicing defect resulting in the omission of exon 20 from the mRNA transcribed from . In this study, we demonstrated that the variant is four nucleotides away from the conventional splicing site, and our findings suggest that splicing mechanisms need to be better understood, as well as how neighbouring regions may impact splicing.