Kim Bong Jik, Jeon Hyoung Won, Jeon Woosung, Han Jin Hee, Oh Jayoung, Yi Nayoung, Kim Min Young, Kim Minah, Kim Justin Namju, Kim Bo Hye, Hyon Joon Young, Kim Dongsup, Koo Ja-Won, Oh Doo-Yi, Choi Byung Yoon
Department of Otolaryngology-Head and Neck Surgery, Chungnam National University College of Medicine, Chungnam National University Sejong Hospital, Sejong, South Korea.
Brain Research Institute, Chungnam National University College of Medicine, Daejeon, South Korea.
J Med Genet. 2022 May;59(5):470-480. doi: 10.1136/jmedgenet-2020-107594. Epub 2021 Mar 22.
Down-sloping sensorineural hearing loss (SNHL) in people in their teens and 20s hampers efficient learning and communication and in-depth social interactions. Nonetheless, its aetiology remains largely unclear, with the exception of some potential causative genes, none of which stands out especially in people in their teens and 20s. Here, we examined the role and genotype-phenotype correlation of lipoxygenase homology domain 1 () in down-sloping SNHL through a cohort study.
Based on the Seoul National University Bundang Hospital (SNUBH) genetic deafness cohort, in which the patients show varying degrees of deafness and different onset ages (n=1055), we have established the 'SNUBH Teenager-Young Adult Down-sloping SNHL' cohort (10-35 years old) (n=47), all of whom underwent exome sequencing. Three-dimensional molecular modelling, minigene splicing assay and short tandem repeat marker genotyping were performed, and medical records were reviewed.
accounted for 33.3% of all genetically diagnosed cases of down-sloping SNHL (n=18) and 12.8% of cases in the whole down-sloping SNHL cohort (n=47) of young adults. We identified a potential common founder allele, as well as an interesting genotype-phenotype correlation. We also showed that transcript 6 is necessary and probably sufficient for normal hearing.
exceeds other genes in its contribution to down-sloping SNHL in young adults, rising as a signature causative gene, and shows a potential but interesting genotype-phenotype correlation.
十几岁和二十几岁人群中的下坡型感音神经性听力损失（SNHL）会妨碍高效学习、交流及深入的社交互动。尽管如此，其病因在很大程度上仍不明确，除了一些潜在的致病基因外，在十几岁和二十几岁的人群中没有一个基因特别突出。在此，我们通过一项队列研究探讨了脂氧合酶同源结构域1（）在青少年下坡型SNHL中的作用及基因型-表型相关性。
基于首尔国立大学盆唐医院（SNUBH）遗传性耳聋队列（其中患者表现出不同程度的耳聋和不同的发病年龄，n = 1055），我们建立了“SNUBH青少年-青年下坡型SNHL”队列（10 - 35岁）（n = 47），所有患者均接受了外显子组测序。进行了三维分子建模、小基因剪接分析和短串联重复标记基因分型，并查阅了病历。
在所有基因诊断的下坡型SNHL病例（n = 18）中占33.3%，在整个青年下坡型SNHL队列（n = 47）中占12.8%。我们鉴定出一个潜在的共同始祖等位基因，以及一种有趣的基因型-表型相关性。我们还表明转录本6对正常听力是必要的，可能也是充分的。
在对青年下坡型SNHL的贡献方面超过其他基因，成为一个标志性致病基因，并显示出潜在但有趣的基因型-表型相关性。
