Diagnostic Application of Targeted Next-Generation Sequencing of 80 Genes Associated with Disorders of Sexual Development.
Diagnostic Application of Targeted Next-Generation Sequencing of 80 Genes Associated with Disorders of Sexual Development.
复制标题
与性发育障碍相关的 80 个基因的靶向下一代测序的诊断应用
DOI：
10.1038/srep44536
复制
发表时间：
2017-03-15
影响因子：
4.6
通讯作者：
Yu Y
中科院分区：
文献类型：
--
作者：
Fan Y;Zhang X;Wang L;Wang R;Huang Z;Sun Y;Yao R;Huang X;Ye J;Han L;Qiu W;Zhang H;Liang L;Gu X;Yu Y
性发育障碍（DSD）估计发生在1 4500出生。由于DSD的遗传病因是高度异质性的，通过单基因检测获得明确的分子诊断具有挑战性。利用高通量测序的前期提出了一种有效的方法来帮助诊断。本研究旨在检查下一代测序在DSD中的诊断率。选择了32名先前接受过临床检查和单基因检测的DSD患者，有或没有诊断。之前的单基因测试被掩蔽，然后样本经过80个基因的靶向下一代测序，从中评估诊断率。从32名患者中的9名获得了可能的诊断，鉴定了致病性或可能致病性变体（即，28.1%，而单基因检测为10%）。在另外5名患者（15.6%）中，发现了意义不确定的变异。17个单核苷酸变异和一个小的缺失），8个以前没有报道过。这项研究支持了下一代测序可以成为DSD临床诊断和变异发现的有效工具的观点。
Disorders of sexual development (DSD) are estimated to occur in 1 of 4500 births. Since the genetic etiology of DSD is highly heterogeneous, obtaining a definitive molecular diagnosis by single gene test is challenging. Utilizing a high-throughput sequencing upfront is proposed as an efficient approach to aid in the diagnosis. This study aimed to examine the diagnostic yield of next-generation sequencing in DSD. 32 DSD patients that previously received clinical examinations and single gene tests were selected, with or without a diagnosis. Prior single gene tests were masked, and then samples went through targeted next-generation sequencing of 80 genes from which the diagnostic yield was assessed. A likely diagnosis, with pathogenic or likely pathogenic variants identified, was obtained from nine of the 32 patients (i.e., 28.1%, versus 10% by single gene tests). In another five patients (15.6%), variants of uncertain significance were found. Among 18 variants identified (i.e., 17 single nucleotide variants and one small deletion), eight had not been previously reported. This study supports the notion that next-generation sequencing can be an efficient tool in the clinical diagnosis and variant discovery in DSD.