Molecular diagnostic experience of whole-exome sequencing in adult patients
Jennifer E. Posey , Jill A. Rosenfeld , Regis A. James , Matthew Bainbridge , Zhiyv Niu , Xia Wang , Shweta Dhar , Wojciech Wiszniewski , Zeynep H. C. Akdemir , Tomasz Gambin , Fan Xia , Richard E. Person , Magdalena Walkiewicz , Chad A. Shaw , V. Reid Sutton , Arthur L. Beaudet , Donna Muzny , Christine M. Eng , Yaping Yang , Richard A. Gibbs , James R. Lupski , Eric Boerwinkle , Sharon E. Plon
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.
|Journal series||Genetics in Medicine, ISSN 1098-3600|
|Publication size in sheets||0.5|
|Keywords in English||adult patients; whole-exome sequencing|
|Score|| = 40.0, 15-05-2020, ArticleFromJournal|
= 40.0, 15-05-2020, ArticleFromJournal
|Publication indicators||= 83; = 82; = 113.0; : 2016 = 2.529; : 2016 = 8.229 (2) - 2016=7.437 (5)|
|Citation count*||113 (2020-05-11)|
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.