Intronic OTOF mutation causes an atypical splicing defect resulting in auditory neuropathy spectrum disorder
SANAZ MOHAMMADI HOSSEIN JAFARI KHAMIRANI SINA ZOGHI SEYED ALIREZA DASTGHEIB SEYED MOHAMMAD BAGHER TABEI MAHDIEH TALEBZADEH MOHAMMAD HOSSEIN ADIBI MEHDI DIANATPOUR
Click here to view fulltext PDF
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.
SANAZ MOHAMMADI1 HOSSEIN JAFARI KHAMIRANI2 SINA ZOGHI3 SEYED ALIREZA DASTGHEIB2 SEYED MOHAMMAD BAGHER TABEI2 4 MAHDIEH TALEBZADEH5 MOHAMMAD HOSSEIN ADIBI6 MEHDI DIANATPOUR2 7
Volume 102, 2023
Continuous Article Publishing mode
Click here for Editorial Note on CAP Mode