Exome Sequencing Reveals De Novo Variants in Congenital Scoliosis
Exome Sequencing Reveals De Novo Variants in Congenital Scoliosis
复制标题
DOI：
10.1055/s-0041-1726282
复制
发表时间：
2021-04
影响因子：
0.4
通讯作者：
Kohei Murakami;Shingo Kikugawa;Shoji Seki;H. Terai;Takako Suzuki;Masaki Nakano;J. Takahashi;Yukio Nakamura
中科院分区：
文献类型：
--
作者：
Kohei Murakami;Shingo Kikugawa;Shoji Seki;H. Terai;Takako Suzuki;Masaki Nakano;J. Takahashi;Yukio Nakamura
摘要先天性脊柱侧凸（CS）是一种以脊柱异常为特征的脊柱侧弯。TBX 6基因中的致病性遗传变异是CS的原因之一。然而，由于许多临床诊断的CS病例没有已知的TBX 6基因变异，本研究旨在通过外显子组测序（ES）来发现与CS疾病易感性相关的新基因。本研究在5个日本CS患者及其健康父母或姐妹的队列中采用ES，共5个家庭中的16个样本。使用SIFT、PolyPhen-2、Mutation Taster和CADD进行变体解读。通过ES鉴定了4种新生变体，并通过桑格测序确认：1种移码变体（SHISA 3）和3种错义变体（AGBL 5、HDAC 4和PDE 2A）。ES还在MOCOS基因中发现了1个纯合变体。通过SIFT、PolyPhen-2、Mutation Taster和/或CADD预测所有这些变体都是有害的。在这项研究中发现的新生变异的数量正是偶然预期的。需要进行额外的功能研究或使用基因匹配器收集匹配的患者。
Abstract Congenital scoliosis (CS) is a lateral curvature of the spine characterized by the presence of vertebral anomalies. Pathogenic genetic variants in the TBX6 gene are one of the causes of CS. However, since many clinically diagnosed cases of CS are without known TBX6 gene variations, this study aims to uncover new genes related to disease susceptibility of CS by exome sequencing (ES). This study employed ES in a cohort of 5 Japanese patients with CS and their healthy parents or a sister for a total of 16 samples among 5 families. Variant interpretation was performed using SIFT, PolyPhen-2, Mutation Taster, and CADD. Four de novo variants were identified by ES and confirmed by Sanger sequencing: 1 frameshift variant (SHISA3) and 3 missense variants (AGBL5, HDAC4, and PDE2A). ES also uncovered 1 homozygous variant in the MOCOS gene. All of these variants were predicted to be deleterious by SIFT, PolyPhen-2, Mutation Taster, and/or CADD. The number of de novo variants identified in this study was exactly what would be expected by chance. Additional functional studies or gathering matched patients using Gene Matcher are needed.