Stark Zornitza, Tan Tiong Y, Chong Belinda, Brett Gemma R, Yap Patrick, Walsh Maie, Yeung Alison, Peters Heidi, Mordaunt Dylan, Cowie Shannon, Amor David J, Savarirayan Ravi, McGillivray George, Downie Lilian, Ekert Paul G, Theda Christiane, James Paul A, Yaplito-Lee Joy, Ryan Monique M, Leventer Richard J, Creed Emma, Macciocca Ivan, Bell Katrina M, Oshlack Alicia, Sadedin Simon, Georgeson Peter, Anderson Charlotte, Thorne Natalie, Gaff Clara, White Susan M
Murdoch Childrens Research Institute, Melbourne, Australia.
University of Melbourne, Melbourne, Australia.
Genet Med. 2016 Nov;18(11):1090-1096. doi: 10.1038/gim.2016.1. Epub 2016 Mar 3.
To prospectively evaluate the diagnostic and clinical utility of singleton whole-exome sequencing (WES) as a first-tier test in infants with suspected monogenic disease.
Singleton WES was performed as a first-tier sequencing test in infants recruited from a single pediatric tertiary center. This occurred in parallel with standard investigations, including single- or multigene panel sequencing when clinically indicated. The diagnosis rate, clinical utility, and impact on management of singleton WES were evaluated.
Of 80 enrolled infants, 46 received a molecular genetic diagnosis through singleton WES (57.5%) compared with 11 (13.75%) who underwent standard investigations in the same patient group. Clinical management changed following exome diagnosis in 15 of 46 diagnosed participants (32.6%). Twelve relatives received a genetic diagnosis following cascade testing, and 28 couples were identified as being at high risk of recurrence in future pregnancies.
This prospective study provides strong evidence for increased diagnostic and clinical utility of singleton WES as a first-tier sequencing test for infants with a suspected monogenic disorder. Singleton WES outperformed standard care in terms of diagnosis rate and the benefits of a diagnosis, namely, impact on management of the child and clarification of reproductive risks for the extended family in a timely manner.Genet Med 18 11, 1090-1096.
前瞻性评估单例全外显子组测序（WES）作为疑似单基因疾病婴儿的一线检测方法的诊断及临床应用价值。
对来自一家儿科三级中心的婴儿进行单例WES检测作为一线测序检测。同时进行标准检查，包括临床指征明确时的单基因或多基因panel测序。评估单例WES的诊断率、临床应用价值及其对治疗管理的影响。
80例入组婴儿中，46例（57.5%）通过单例WES获得分子遗传学诊断，而同一患者组中接受标准检查的有11例（13.75%）。46例确诊参与者中有15例（32.6%）在全外显子组诊断后治疗管理发生改变。12名亲属在级联检测后获得基因诊断，28对夫妇被确定为未来妊娠复发风险高。
这项前瞻性研究为单例WES作为疑似单基因疾病婴儿的一线测序检测方法在提高诊断及临床应用价值方面提供了有力证据。单例WES在诊断率及诊断益处方面表现优于标准治疗，即对患儿治疗管理的影响以及及时明确大家庭的生殖风险。《遗传医学》18卷11期，1090 - 1096页
