De novo deletions and duplications of 17q25.3 cause susceptibility to XXXX .

@entity1 @entity1700 @entity1757 @entity2461 @entity600 @entity1498 @entity299 @entity118 @entity65
BACKGROUND: Genomic disorders resulting from deletion or duplication of genomic segments are known to be an important cause of @entity65 ( @entity65 ). In our previous study, we identified a unique individual with a de novo 17q25.3 deletion from a study of 714 individuals with CVM. METHODS: To understand the contribution of this locus to cardiac @entity600 , we reviewed the data on 60,000 samples submitted for array comparative genomic hybridization (CGH) studies to Medical Genetics Laboratories at Baylor College of Medicine, and ascertained seven individuals with segmental aneusomy of 17q25. We validated our findings by studying another individual with a de novo submicroscopic deletion of this region from Cytogenetics Laboratory at Cincinnati @entity1 's Hospital. Using bioinformatic analyses including protein-protein interaction network, @entity1 tissue expression patterns, haploinsufficiency scores, and other annotation systems, including a training set of 251 genes known to be linked to @entity1 @entity299 , we constructed a pathogenicity score for cardiac phenotype for each of the 57 genes within the terminal 2.0  Mb of 17q25.3. RESULTS: We found relatively high penetrance of @entity65 (~60  %) with five deletions and three duplications, observed in eight unrelated individuals. Distinct cardiac phenotypes were present in four of these subjects with non-recurrent de novo deletions (range 0.08  Mb-1.4  Mb) in the subtelomeric region of 17q25.3. These included @entity1498 ( @entity1498 ), @entity1700 ( @entity1700 ), @entity1757 ( @entity1757 ) and @entity118 ( @entity118 ). Amongst the three individuals with variable size duplications of this region, one had @entity2461 ( @entity2461 ) at 8  months of age. CONCLUSION: The distinct cardiac lesions observed in the affected @entity1 and the bioinformatics analyses suggest that multiple genes may be plausible drivers of the cardiac phenotype within this gene-rich critical interval of 17q25.3.
