Clinical Whole-Exome Sequencing.pdf

original article T h e n e w e ngl a nd j o u r na l o f m e dic i n e n engl j med 369;16 october 17,Clinical Whole-Exome Sequencing for the Diagnosis of Mendelian Disorders Yaping Yang, Ph.D., Donna M. Muzny, M.Sc., Jeffrey G. Reid, Ph.D., Matthew N. Bainbridge, Ph.D., Alecia Willis, Ph.D., Patricia A. Ward, M.S., Alicia Braxton, M.S., Joke Beuten, Ph.D., Fan Xia, Ph.D., Zhiyv Niu, Ph.D., Matthew Hardison, Ph.D., Richard Person, Ph.D., Mir Reza Bekheirnia, M.D., Magalie S. Leduc, Ph.D., Amelia Kirby, M.D., Peter Pham, M.Sc., Jennifer Scull, Ph.D., Min Wang, Ph.D., Yan Ding, M.D., Sharon E. Plon, M.D., Ph.D., James R. Lupski, M.D., Ph.D., Arthur L. Beaudet, M.D., Richard A. Gibbs, Ph.D., and Christine M. Eng, M.D. From the Departments of Molecular and Human Genetics (Y.Y., A.W., P.A.W., A.B., J.B., F.X., Z.N., M.H., R.P., M.R.B., M.S.L., A.K., J.S., S.E.P., J.R.L., A.L.B., C.M.E.) and Pediatrics (S.E.P., J.R.L.) and the Human Genome Sequencing Center (D.M.M., J.G.R., M.N.B., P.P., M.W., Y.D., J.R.L., R.A.G.), Baylor College of Medicine, Hous- ton. Address reprint requests to Dr. Eng at the Department of Molecular and Hu- man Genetics, NAB 2015, Baylor College of Medicine, Houston, TX 77030, or at ceng@. This article was published on October 2, 2013, at NEJM.org. N Engl J Med 2013;369:1502-11. DOI: 10.1056/NEJMoa1306555 Copyright ? 2013 Massachusetts Medical Society. A BS TR AC T BACKGROUND Whole-exome sequencing is a diagnostic approach for the identification of molecular defects in patients with suspected genetic disorders. METHODS We developed technical, bioinformatic, interpretive, and validation pipelines for whole- exome sequencing in a certified clinical laboratory to identify sequence variants underlying disease phenotypes in patients. RESULTS We present data on the first 250 probands for whom referring physicians ordered whole-exome sequencing. Patients presented with a range of phenotypes suggesting potential