TY - JOUR
T1 - Molecular diagnostic experience of whole-exome sequencing in adult patients
AU - Posey, Jennifer E.
AU - Rosenfeld, Jill A.
AU - James, Regis A.
AU - Bainbridge, Matthew
AU - Niu, Zhiyv
AU - Wang, Xia
AU - Dhar, Shweta
AU - Wiszniewski, Wojciech
AU - Akdemir, Zeynep H.C.
AU - Gambin, Tomasz
AU - Xia, Fan
AU - Person, Richard E.
AU - Walkiewicz, Magdalena
AU - Shaw, Chad A.
AU - Sutton, V. Reid
AU - Beaudet, Arthur L.
AU - Muzny, Donna
AU - Eng, Christine M.
AU - Yang, Yaping
AU - Gibbs, Richard A.
AU - Lupski, James R.
AU - Boerwinkle, Eric
AU - Plon, Sharon E.
N1 - Publisher Copyright:
© American College of Medical Genetics and Genomics.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - 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.
AB - 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.
KW - adult patients
KW - whole-exome sequencing
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U2 - 10.1038/gim.2015.142
DO - 10.1038/gim.2015.142
M3 - Article
C2 - 26633545
AN - SCOPUS:84977147369
SN - 1098-3600
VL - 18
SP - 678
EP - 685
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 7
ER -