Mohammadi Sanaz, Khamirani Hossein Jafari, Zoghi Sina, Dastgheib Seyed Alireza, Bagher Tabei Seyed Mohammad, Talebzadeh Mahdieh, Adibi Mohammad Hossein, Dianatpour Mehdi
Comprehensive Medical Genetic Center, Shiraz University of Medical Sciences, Shiraz 71936-13311, Iran.
J Genet. 2023;102.
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.
基因中的致病性变异会导致听觉神经病谱系障碍（ANSD），即语前非综合征性ANSD和温度敏感性ANSD（TS-ANSD）。所有研究对象均提供了血液样本用于基因分析和测序。进行全外显子组测序以鉴定致病性致病变异。提取RNA以分析由OTOF转录产生的信使RNA（mRNA）。在此，我们鉴定出一个与OTOF相关的ANSD家系。该疾病由基因中的内含子突变（NM_194248: c.2406>4A[G]）引起。在进一步分析中，我们证明该变异导致剪接缺陷，致使从该基因转录的mRNA中缺失外显子20。在本研究中，我们证明该变异距离传统剪接位点有四个核苷酸，我们的研究结果表明，需要更好地理解剪接机制以及邻近区域如何影响剪接。
