Posey Jennifer E, Rosenfeld Jill A, James Regis A, Bainbridge Matthew, Niu Zhiyv, Wang Xia, Dhar Shweta, Wiszniewski Wojciech, Akdemir Zeynep H C, Gambin Tomasz, Xia Fan, Person Richard E, Walkiewicz Magdalena, Shaw Chad A, Sutton V Reid, Beaudet Arthur L, Muzny Donna, Eng Christine M, Yang Yaping, Gibbs Richard A, Lupski James R, Boerwinkle Eric, Plon Sharon E
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, Texas, USA.
Genet Med. 2016 Jul;18(7):678-85. doi: 10.1038/gim.2015.142. Epub 2015 Dec 3.
Whole-exome sequencing (WES) is increasingly used as a diagnostic tool in medicine, but prior reports focus on predominantly pediatric cohorts with neurologic or developmental disorders. We describe the diagnostic yield and characteristics of WES in adults.
We performed a retrospective analysis of consecutive WES reports for adults from a diagnostic laboratory. Phenotype composition was determined using Human Phenotype Ontology terms.
Molecular diagnoses were reported for 17.5% (85/486) of adults, which is lower than that for a primarily pediatric population (25.2%; P = 0.0003); the diagnostic rate was higher (23.9%) for those 18-30 years of age compared to patients older than 30 years (10.4%; P = 0.0001). Dual Mendelian diagnoses contributed to 7% of diagnoses, revealing blended phenotypes. Diagnoses were more frequent among individuals with abnormalities of the nervous system, skeletal system, head/neck, and growth. Diagnostic rate was independent of family history information, and de novo mutations contributed to 61.4% of autosomal dominant diagnoses.
Early WES experience in adults demonstrates molecular diagnoses in a substantial proportion of patients, informing clinical management, recurrence risk, and recommendations for relatives. A positive family history was not predictive, consistent with molecular diagnoses often revealed by de novo events, informing the Mendelian basis of genetic disease in adults.Genet Med 18 7, 678-685.
全外显子组测序（WES）在医学领域越来越多地被用作一种诊断工具，但先前的报告主要集中在患有神经或发育障碍的儿科队列。我们描述了成人WES的诊断率及特征。
我们对一家诊断实验室连续的成人WES报告进行了回顾性分析。使用人类表型本体术语确定表型组成。
报告显示17.5%（85/486）的成人有分子诊断结果，低于主要为儿科人群的诊断率（25.2%；P = 0.0003）；18至30岁人群的诊断率（23.9%）高于30岁以上患者（10.4%；P = 0.0001）。双重孟德尔诊断占诊断结果的7%，揭示了混合表型。在神经系统、骨骼系统、头/颈部及生长异常的个体中，诊断更为常见。诊断率与家族史信息无关，新发突变占常染色体显性诊断的61.4%。
成人早期WES经验表明，相当一部分患者有分子诊断结果，可为临床管理、复发风险及亲属建议提供依据。阳性家族史并无预测性，这与新发事件常揭示分子诊断结果一致，为成人遗传疾病的孟德尔基础提供了依据。《基因医学》18卷7期，678 - 685页
