|Title||Molecular diagnostic experience of whole-exome sequencing in adult patients.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Posey, JE, Rosenfeld, JA, James, RA, Bainbridge, MN, Niu, Z, Wang, X, Dhar, S, Wiszniewski, W, Akdemir, ZHC, Gambin, T, Xia, F, Person, RE, Walkiewicz, M, Shaw, CA, V Sutton, R, Beaudet, AL, Muzny, DM, Eng, CM, Yang, Y, Gibbs, RA, Lupski, JR, Boerwinkle, E, Plon, SE|
|Date Published||2016 Jul|
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.Genet Med 18 7, 678-685.
|Alternate Journal||Genet. Med.|
|PubMed Central ID||PMC4892996|
|Grant List||U54 HG006542 / HG / NHGRI NIH HHS / United States |
T32 GM007526 / GM / NIGMS NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
U01 HG006485 / HG / NHGRI NIH HHS / United States
K23 NS078056 / NS / NINDS NIH HHS / United States
R01 NS058529 / NS / NINDS NIH HHS / United States