Abstract：
Clinical exome sequencing (CES) has shown great utility in the diagnosis of Mendelian disorders. CES can unravel secondary findings (SFs) unrelated to the primary diagnosis but with potential health implications. The American College of Medical Genetics and Genomics (ACMG) has published a guideline for reporting secondary findings and recently updated an ACMG SF v3.0 list comprising 73 genes. Several studies have been performed to explore the prevalence of SFs. However, the data were limited in the Chinese population. In this study, we evaluated the genetic data of 2987 individuals from the Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study group in accordance with the ACMG SF v3.0 list. The detected variants were evaluated using the ACMG classification guidelines, HGMD, and ClinVar database. Totally, 157 (157/2987, 5.3%) individuals had reportable variants within genes associated with cancer, cardiovascular, metabolic, and miscellaneous phenotypes. We identified 63 known pathogenic (KP) variants in 72 individuals (72/2987, 2.4%) and 96 expected pathogenic (EP) variants in 105 individuals (3.5%). Forty-five individuals carried SFs in v3.0 newly added genes, which accounted for 1.5% of our cohort. Our findings could contribute to existing knowledge of secondary findings in different ethnicities and indicate the necessity for clinicians to update the SFs gene list.
摘要：
临床外显子组测序（CES）在孟德尔疾病诊断中显示出巨大的实用性。CES可以解开与主要诊断无关的次要发现（SF），但具有潜在的健康影响。美国医学遗传学和基因组学学院（ACMG）发布了报告次要发现的指南，最近更新了包含73个基因的ACMGSFv3.0列表。已经进行了几项研究来探索SF的患病率。然而,这些数据在中国人群中是有限的。在这项研究中,我们根据ACMGSFv3.0列表评估了涉及脊柱侧凸和合并疾病的解密障碍(DISCO)研究组的2987名个体的遗传数据.使用ACMG分类指南评估检测到的变异，HGMD,和ClinVar数据库。完全正确,157（157/2987，5.3%）个体在与癌症相关的基因中有可报告的变异，心血管,新陈代谢，和各种表型。我们在72个个体（72/2987，2.4％）中鉴定了63个已知致病性（KP）变体，在105个个体（3.5％）中鉴定了96个预期致病性（EP）变体。45个人在v3.0新添加的基因中携带SF，占我们队列的1.5%。我们的发现可能有助于对不同种族的次要发现的现有知识，并表明临床医生有必要更新SF基因列表。
