Pathogenic variants in OTOF 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 OTOF (NM_194248: c.2406?4A[G). In further analysis, we proved
that this variant causes a splicing defect resulting in theomission of exon 20 from the mRNA transcribed from OTOF.
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.