College of Medicine, National Taiwan University, Taipei, Taiwan.
Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Mol Genet Genomic Med. 2020 Oct;8(10):e1455. doi: 10.1002/mgg3.1455. Epub 2020 Aug 14.
Exome sequencing has recently become more readily available, and more information about incidental findings has been disclosed. However, data from East Asia are scarce. We studied the application of exome sequencing to the identification of pathogenic/likely pathogenic variants in the ACMG 59 gene list and the frequency of these variants in the Taiwanese population.
This study screened 161 Taiwanese exomes for variants from the ACMG 59 gene list. The identified variants were reviewed based on information from different databases and the available literature and classified according to the ACMG standard guidelines.
We identified seven pathogenic/likely pathogenic variants in eight individuals, with five participants with autosomal recessive variants in one allele and three participants with autosomal dominant variants. Approximately 1.86% (3/161) of the Taiwanese individuals had a reportable pathogenic/likely pathogenic variant as determined by whole-exome sequencing (WES), which was comparable to the proportions published previously in other countries. We further investigated the high carrier rate of rare variants in the ATP7B gene, which might indicate a founder effect in our population.
This study was the first to provide Taiwanese population data of incidental findings and emphasized a high carrier rate of candidate pathogenic/likely pathogenic variants in the ATP7B gene.
外显子组测序技术最近变得更加普及，更多的偶然发现信息也被披露。然而，东亚地区的数据仍然相对较少。本研究旨在探讨外显子组测序技术在识别 ACMG59 基因列表中的致病性/可能致病性变异以及这些变异在台湾人群中的频率方面的应用。
本研究对 161 例台湾人的外显子组进行了 ACMG59 基因列表中的变异筛选。根据不同数据库和现有文献中的信息对鉴定出的变异进行了回顾，并根据 ACMG 标准指南进行了分类。
我们在 8 个人中发现了 7 个致病性/可能致病性变异，其中 5 人在一个等位基因中存在常染色体隐性变异，3 人存在常染色体显性变异。通过全外显子组测序（WES）确定，大约有 1.86%（3/161）的台湾个体存在可报告的致病性/可能致病性变异，这与之前在其他国家发表的比例相当。我们进一步研究了 ATP7B 基因中罕见变异的高携带率，这可能表明在我们的人群中存在一个遗传起源。
本研究首次提供了台湾人群的偶然发现数据，并强调了 ATP7B 基因中候选致病性/可能致病性变异的高携带率。
