Lee Eric, Orton Kaylee, Kwan Edward, Faga Claire, Le Trang, Shaheen Ranad, Nair Vivek, Cliffe Simon
Molecular Genetics Department, Virtus Diagnostics, Suite 4, Level 1, 20-30 Blamey St, Revesby, NSW 2212, Australia.
Genes (Basel). 2025 May 30;16(6):671. doi: 10.3390/genes16060671.
: The clinical utility of reproductive carrier screening varies based on the genes tested, variant reporting policies, and the screened patient population. This study aims to evaluate the outcomes of carrier screening among reproductive couples undergoing testing in a routine clinical setting. : A total of 1595 couples, primarily referred by reproductive endocrinology and infertility specialists, underwent couple-based carrier screening across 390 genes. Carrier states were assessed on a couple basis and reported only if a couple were at risk of having affected offspring. At-risk conditions were classified by severity, as well as their likelihood of clinical impact based on the specific variants detected in each at-risk couple. Secondary findings with potential personal utility were also evaluated. : Among the screened couples, 4.2% were at risk of having a child with a genetic condition. When limited to high-clinical-impact results, the at-risk couple rate decreased to 1.0%, with 44% of these cases involving , , or . Secondary findings were identified in 1.7% of individuals. : Carrier screening for only , , and will miss more than half of at-risk couples, underscoring the importance of broader carrier screening. Specific variants and their combinations can influence the predicted clinical impact of at-risk conditions, marking a key advantage of couple-based reporting. Secondary findings were common, highlighting the importance of discussing these potential findings during pre-test counselling.
生殖携带者筛查的临床效用因检测的基因、变异报告政策以及筛查的患者群体而异。本研究旨在评估在常规临床环境中接受检测的生殖夫妇中携带者筛查的结果。
共有1595对夫妇，主要由生殖内分泌与不孕症专家转诊，对390个基因进行了夫妇双方的携带者筛查。携带者状态是基于夫妇双方进行评估的，只有当一对夫妇有生育患病后代的风险时才会报告。根据严重程度以及基于每对有风险夫妇中检测到的特定变异对临床影响的可能性，对有风险的情况进行分类。还评估了具有潜在个人效用的次要发现。
在接受筛查的夫妇中，4.2%有生育患有遗传疾病孩子的风险。当仅限于具有高临床影响的结果时，有风险的夫妇比例降至1.0%，其中44%的病例涉及[此处原文缺失具体疾病名称]、[此处原文缺失具体疾病名称]或[此处原文缺失具体疾病名称]。在1.7%的个体中发现了次要发现。
仅对[此处原文缺失具体疾病名称]、[此处原文缺失具体疾病名称]和[此处原文缺失具体疾病名称]进行携带者筛查会遗漏超过一半的有风险夫妇，这凸显了更广泛携带者筛查的重要性。特定变异及其组合可影响有风险情况的预测临床影响，这标志着基于夫妇报告的一个关键优势。次要发现很常见，突出了在检测前咨询期间讨论这些潜在发现的重要性。
