期刊
GENETICS IN MEDICINE
卷 18, 期 7, 页码 678-685出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/gim.2015.142
关键词
adult patients; whole-exome sequencing
资金
- Medical Genetics Research Fellowship Program NIH/NIGMS [NIH T32 GM07526]
- National Institute of Neurological Disorders and Stroke (NINDS) [K23NS078056]
- National Human Genome Research Institute (NHGRI) [U01 HG006485]
- National Cancer Institute (NCI)
- NHGRI and National Heart, Lung, and Blood Institute (NHLBI) [U54 HG006542]
- NHGRI [U54-HG003273]
- NINDS [R01 NS058529]
Purpose: 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. Methods: We performed a retrospective analysis of consecutive WES reports for adults from a diagnostic laboratory. Phenotype composition was determined using Human Phenotype Ontology terms. Results: 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. Conclusion: 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据