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.

Author Jennifer E. Posey - [Baylor College of Medicine]
Jennifer E. Posey,,
, Jill A. Rosenfeld - [Baylor College of Medicine]
Jill A. Rosenfeld,,
, Regis A. James - [Baylor College of Medicine]
Regis A. James,,
, Matthew Bainbridge - [Baylor College of Medicine]
Matthew Bainbridge,,
, Zhiyv Niu - [Baylor College of Medicine]
Zhiyv Niu,,
, Xia Wang - [Baylor College of Medicine]
Xia Wang,,
, Shweta Dhar - [Baylor College of Medicine]
Shweta Dhar,,
, Wojciech Wiszniewski - [Baylor College of Medicine]
Wojciech Wiszniewski ,,
, Zeynep H. C. Akdemir - [Baylor College of Medicine]
Zeynep H. C. Akdemir,,
, Tomasz Gambin (FEIT / IN) - [Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA]
Tomasz Gambin,,
- The Institute of Computer Science
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
et al.`
Journal seriesGenetics in Medicine, ISSN 1098-3600
Issue year2016
Publication size in sheets0.5
Keywords in Englishadult patients; whole-exome sequencing
ASJC Classification2716 Genetics(clinical)
Languageen angielski
Score (nominal)40
Score sourcejournalList
ScoreMinisterial score = 40.0, 27-08-2020, ArticleFromJournal
Ministerial score (2013-2016) = 40.0, 27-08-2020, ArticleFromJournal
Publication indicators WoS Citations = 83; Scopus Citations = 82; GS Citations = 124.0; Scopus SNIP (Source Normalised Impact per Paper): 2016 = 2.529; WoS Impact Factor: 2016 = 8.229 (2) - 2016=7.437 (5)
Citation count*128 (2020-08-30)
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