Huang Qinlin, Wang Zhongjie, Teng Yanling, Zhang Wen, Wen Juan, Zhu Huimin, Liang Desheng, Wu Lingqian, Li Zhuo
Center for Medical Genetics, Hunan Key Laboratory of Medical Genetics, MOE Key Lab of Rare Pediatric Diseases, School of Life Sciences, Central South University, Changsha, China.
Laboratory of Molecular Genetics, Hunan Jiahui Genetics Hospital, Changsha, China.
Front Genet. 2024 Jun 24;15:1415811. doi: 10.3389/fgene.2024.1415811. eCollection 2024.
This study aimed to screen the genetic etiology for the high-risk families including those with an adverse pregnancy history, a history of consanguineous marriages, or a history of genetic diseases, but lack of proband via whole exome sequencing (WES).
128 individuals from high-risk family were tested by WES. The candidate variants were analyzed according to the ACMG criteria to screen the potential carriers. At-risk couples (ARCs) who harbored the same causative gene were provided with precise fertility guidance to avoid the birth of children with birth defects.
The total detection rate was 36.72%, with pathogenic/likely pathogenic (P/LP) variants found in 47 individuals, and variants of uncertain significance (VUS) were found in 34. Among couples with adverse pregnancy history: P/LP variants were found in 38 individuals, and VUS were found in 26, for a detection rate of 34.55%; among members of family history of genetic disease or consanguineous marriages: P/LP variants were found in nine individuals, and VUS were found in 8, for a detection rate of 50.00%. Otherwise, we detected 19 ARCs who both carried P/LP variants in the same gene, with a theoretical offspring prevalence of up to 7.42%.
In the absence of probands, carrier screening using WES can provide an efficient tool for screening the molecular etiology of high-risk families.
本研究旨在通过全外显子组测序（WES）筛查包括有不良孕产史、近亲结婚史或遗传病史但缺乏先证者的高危家庭的遗传病因。
对128名来自高危家庭的个体进行WES检测。根据美国医学遗传学与基因组学学会（ACMG）标准分析候选变异，以筛查潜在携带者。为携带相同致病基因的高危夫妇（ARCs）提供精准的生育指导，以避免出生缺陷患儿的出生。
总检出率为36.72%，47名个体中发现了致病/可能致病（P/LP）变异，34名个体中发现了意义未明的变异（VUS）。在有不良孕产史的夫妇中：38名个体发现了P/LP变异，26名个体发现了VUS，检出率为34.55%；在有遗传病史或近亲结婚家族成员中：9名个体发现了P/LP变异，8名个体发现了VUS，检出率为50.00%。此外，我们检测到19对高危夫妇双方均携带同一基因的P/LP变异，其理论后代患病率高达7.42%。
在先证者缺失的情况下，使用WES进行携带者筛查可为筛查高危家庭的分子病因提供一种有效的工具。
