Candidate-gene criteria for clinical reporting: diagnostic exome sequencing identifies altered candidate genes among 8% of patients with undiagnosed diseases.

Genet Med 2017 02 11;19(2):224-235. Epub 2016 Aug 11.

Department of Clinical Genomics, Ambry Genetics, Aliso Viejo, California, USA.

Purpose: Diagnostic exome sequencing (DES) is now a commonly ordered test for individuals with undiagnosed genetic disorders. In addition to providing a diagnosis for characterized diseases, exome sequencing has the capacity to uncover novel candidate genes for disease.

Methods: Family-based DES included analysis of both characterized and novel genetic etiologies. To evaluate candidate genes for disease in the clinical setting, we developed a systematic, rule-based classification schema.

Results: Testing identified a candidate gene among 7.7% (72/934) of patients referred for DES; 37 (4.0%) and 35 (3.7%) of the genes received evidence scores of "candidate" and "suspected candidate," respectively. A total of 71 independent candidate genes were reported among the 72 patients, and 38% (27/71) were subsequently corroborated in the peer-reviewed literature. This rate of corroboration increased to 51.9% (27/52) among patients whose gene was reported at least 12 months previously.

Conclusions: Herein, we provide transparent, comprehensive, and standardized scoring criteria for the clinical reporting of candidate genes. These results demonstrate that DES is an integral tool for genetic diagnosis, especially for elucidating the molecular basis for both characterized and novel candidate genetic etiologies. Gene discoveries also advance the understanding of normal human biology and more common diseases.Genet Med 19 2, 224-235.

Download full-text PDF

Source
http://dx.doi.org/10.1038/gim.2016.95DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5303763PMC
February 2017
19 Reads

Publication Analysis

Top Keywords

candidate genes
20
exome sequencing
12
characterized novel
8
diagnostic exome
8
novel candidate
8
genetic etiologies
8
clinical reporting
8
criteria clinical
8
candidate
7
genes
6
total independent
4
peer-reviewed literature
4
candidate" total
4
"candidate" "suspected
4
scores "candidate"
4
literature rate
4
"suspected candidate"
4
independent candidate
4
evidence scores
4
corroborated peer-reviewed
4

Similar Publications