@article {323, title = {Incidental copy-number variants identified by routine genome testing in a clinical population.}, journal = {Genet Med}, volume = {15}, year = {2013}, month = {2013 Jan}, pages = {45-54}, abstract = {

PURPOSE: Mutational load of susceptibility variants has not been studied on a genomic scale in a clinical population, nor has the potential to identify these mutations as incidental findings during clinical testing been systematically ascertained.

METHODS: Array comparative genomic hybridization, a method for genome-wide detection of DNA copy-number variants, was performed clinically on DNA from 9,005 individuals. Copy-number variants encompassing or disrupting single genes were identified and analyzed for their potential to confer predisposition to dominant, adult-onset disease. Multigene copy-number variants affecting dominant, adult-onset cancer syndrome genes were also assessed.

RESULTS: In our cohort, 83 single-gene copy-number variants affected 40 unique genes associated with dominant, adult-onset disorders and unrelated to the patients{\textquoteright} referring diagnoses (i.e., incidental) were found. Fourteen of these copy-number variants are likely disease-predisposing, 25 are likely benign, and 44 are of unknown clinical consequence. When incidental copy-number variants spanning up to 20 genes were considered, 27 copy-number variants affected 17 unique genes associated with dominant, adult-onset cancer predisposition.

CONCLUSION: Copy-number variants potentially conferring susceptibility to adult-onset disease can be identified as incidental findings during routine genome-wide testing. Some of these mutations may be medically actionable, enabling disease surveillance or prevention; however, most incidentally observed single-gene copy-number variants are currently of unclear significance to the patient.

}, keywords = {Age of Onset, Base Sequence, Chromosome Mapping, Comparative Genomic Hybridization, DNA Copy Number Variations, Female, Gene Order, Genetic Predisposition to Disease, Humans, Inheritance Patterns, Male, Reproducibility of Results}, issn = {1530-0366}, doi = {10.1038/gim.2012.95}, author = {Boone, Philip M and Soens, Zachry T and Campbell, Ian M and Stankiewicz, Pawel and Cheung, Sau Wai and Patel, Ankita and Beaudet, Arthur L and Plon, Sharon E and Shaw, Chad A and McGuire, Amy L and Lupski, James R} }