Genomic sequencing identifies secondary findings in a cohort of parent study participants
Genomic sequencing identifies secondary findings in a cohort of parent study participants
复制标题
DOI：
10.1038/gim.2018.53
复制
发表时间：
2018-12-01
影响因子：
8.8
通讯作者：
Cooper, Gregory M.
中科院分区：
文献类型：
--
作者：
Thompson, Michelle L.;Finnila, Candice R.;Cooper, Gregory M.
目的：在有发育迟缓和智力障碍儿童的父母中鉴定出临床相关的次要变异。方法：对 789 名“未受影响”的父母进行外显子组/基因组测序和分析。结果：在 25 名个体 (3.2%) 的 21 个基因中鉴定出致病性/可能致病性变异，其中 11 名 (1.4%) 参与者携带由美国医学遗传学和基因组学定义为临床可操作的基因变异。这 25 个人自我报告了相关的临床诊断 (5)；相关家族史或症状（13）；或没有相关家族史、症状或临床诊断 (7)。进行了有限的携带者筛选，在 48 位（6.1%）父母中产生了 15 个变异。还对父母进行了配偶对分析（n = 365），以确定父母双方均为相同隐性疾病携带者的病例，产生了 3 例此类病例（0.8%），其中 2 例的子女患有相关隐性疾病。四名参与者有两项发现（一名携带者和一名非携带者变异）。总共，789 名登记家长中的 71 名 (9.0%) 收到了次要发现。结论：我们提供了临床相关次要发现的比率和类型的概述，这可能有助于设计和实施研究和临床测序工作，以确定此类发现。
Purpose: Clinically relevant secondary variants were identified in parents enrolled with a child with developmental delay and intellectual disability.Methods: Exome/genome sequencing and analysis of 789 "unaffected" parents was performed.Results: Pathogenic/likely pathogenic variants were identified in 21 genes within 25 individuals (3.2%), with 11 (1.4%) participants harboring variation in a gene defined as clinically actionable by the American College of Medical Genetics and Genomics. These 25 individuals self-reported either relevant clinical diagnoses (5); relevant family history or symptoms (13); or no relevant family history, symptoms, or clinical diagnoses (7). A limited carrier screen was performed yielding 15 variants in 48 (6.1%) parents. Parents were also analyzed as mate pairs (n = 365) to identify cases in which both parents were carriers for the same recessive disease, yielding three such cases (0.8%), two of which had children with the relevant recessive disease. Four participants had two findings (one carrier and one noncarrier variant). In total, 71 of the 789 enrolled parents (9.0%) received secondary findings.Conclusion: We provide an overview of the rates and types of clinically relevant secondary findings, which may be useful in the design and implementation of research and clinical sequencing efforts to identify such findings.