Molecular diagnostic experience of whole-exome sequencing in adult patients.

TitleMolecular diagnostic experience of whole-exome sequencing in adult patients.
Publication TypeJournal Article
Year of Publication2016
AuthorsPosey, 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
JournalGenet Med
Date Published2016 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 JournalGenet. Med.
PubMed ID26633545
PubMed Central IDPMC4892996
Grant ListU54 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