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Genet Med. 2016 Jul;18(7):678-85. doi: 10.1038/gim.2015.142. Epub 2015 Dec 3.

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

Author information

1
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
2
Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, Texas, USA.
3
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
4
Baylor Miraca Genetics Laboratories, Baylor College of Medicine, Houston, Texas, USA.
5
Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
6
Department of Pediatrics, Texas Children's Hospital, Houston, Texas, USA.
7
Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
8
Human Genetics Center, University of Texas Health Science Center, Houston, Texas, USA.
9
Texas Children's Cancer Center, Texas Children's Hospital, Houston, Texas, USA.

Abstract

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.

PMID:
26633545
PMCID:
PMC4892996
DOI:
10.1038/gim.2015.142
[Indexed for MEDLINE]
Free PMC Article

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