Comprehensive carrier genetic test using next-generation deoxyribonucleic acid sequencing in infertile couples wishing to conceive through assisted reproductive technology
Comprehensive carrier genetic test using next-generation deoxyribonucleic acid sequencing in infertile couples wishing to conceive through assisted reproductive technology
复制标题
DOI：
10.1016/j.fertnstert.2015.07.1166
复制
发表时间：
2015-11-01
影响因子：
6.7
通讯作者：
Simon, Carlos
中科院分区：
文献类型：
--
作者：
Martin, Julio;Asan;Simon, Carlos
目的：为了开发一种用于辅助生殖技术（ART）患者和供体的扩大的泛种族前概念携带者遗传筛查测试。设计：对从2，570个分析中获得的结果进行回顾性分析。设置：生殖遗传实验室。患者：2，570个样本包括来自配子供体计划的1，170个个体。1，124名个体对应于接受捐赠配子的患者的伴侣;以及来自138对夫妇的276名个体使用自己的配子寻求ART。干预：无。主要结果测量：下一代测序涉及严重儿童表型的549个隐性和X连锁基因，并通过五种互补测试加强，涵盖下一代测序未检测到的高流行突变。临床前验证包括48个携带27个基因已知突变的DNA样本，灵敏度为99%。在临床数据集中，2，161份样本（84%）检测呈阳性，平均每个样本的携带者负担为2.3。在使用自己配子的夫妇中，有5%的人被发现有致病性变异，这可能导致六种不同疾病的高风险。这些高危夫妇和患者接受遗传咨询和建议进行植入前遗传学诊断。对于接受配子捐赠的患者，我们应用了基因检测和盲法匹配系统，以避免高风险组合，无论其携带者负担如何。在女性捐献者中，1.94%的人对X连锁疾病呈阳性;她们接受了遗传咨询，并被丢弃。我们开发了一种全面的携带者遗传筛查测试，结合我们的匹配系统和遗传咨询，构成了一个强大的工具，以避免超过600孟德尔疾病的后代接受艺术的患者。2015年，美国生殖医学会（American Society for Reproductive Medicine）
Objective: To develop an expanded pan-ethnic preconception carrier genetic screening test for use in assisted reproductive technology (ART) patients and donors.Design: Retrospective analysis of results obtained from 2,570 analyses.Setting: Reproductive genetic laboratory.Patient(s): The 2,570 samples comprised 1,170 individuals from the gamete donor programs; 1,124 individuals corresponding to the partner of the patient receiving the donated gamete; and 276 individuals from 138 couples seeking ART using their own gametes.Intervention(s): None.Main Outcome Measure(s): Next-generation sequencing of 549 recessive and X-linked genes involved in severe childhood phenotypes reinforced with five complementary tests covering high prevalent mutations not detected by next-generation sequencing.Result(s): Preclinical validation included 48 DNA samples carrying known mutations for 27 genes, resulting in a sensitivity of 99%. In the clinical dataset, 2,161 samples (84%) tested positive, with an average carrier burden of 2.3 per sample. Five percent of the couples using their own gametes were found to have pathogenic variants conferring high risk for six different diseases. These high-risk couples and patients received genetic counseling and recommendations for preimplantation genetic diagnosis. For patients receiving gamete donation, we applied a genetic testing and blinded matching system to avoid high-risk combinations regardless of their carrier burden. For female donors, 1.94% were positive for X-linked conditions; they received genetic counselling and were discarded.Conclusion(s): We have developed a comprehensive carrier genetic screening test that, combined with our matching system and genetic counseling, constitutes a powerful tool to avoid more than 600 mendelian diseases in the offspring of patients undergoing ART. (C) 2015 by American Society for Reproductive Medicine.