|Title||Incidental copy-number variants identified by routine genome testing in a clinical population.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Boone, PM, Soens, ZT, Campbell, IM, Stankiewicz, P, Cheung, SWai, Patel, A, Beaudet, AL, Plon, SE, Shaw, CA, McGuire, AL, Lupski, JR|
|Date Published||2013 Jan|
|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|
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' 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.
|Alternate Journal||Genet. Med.|
|PubMed Central ID||PMC3705759|
|Grant List||U54 HG006542 / HG / NHGRI NIH HHS / United States |
R01NS058529 / NS / NINDS NIH HHS / United States
U54HG006542 / HG / NHGRI NIH HHS / United States
R01CA138836 / CA / NCI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
R01 CA138836 / CA / NCI NIH HHS / United States
T32GM007330 / GM / NIGMS NIH HHS / United States
T32 GM007330 / GM / NIGMS NIH HHS / United States
R01 NS058529 / NS / NINDS NIH HHS / United States
T32EY007102 / EY / NEI NIH HHS / United States
T32 EY007102 / EY / NEI NIH HHS / United States