Unexpected findings in XXXX predisposition genes detected by array comparative genomic hybridisation: what are the issues?

@entity1 @entity5 @entity245 @entity600 @entity854
OBJECTIVE: To calculate and discuss the percentage of imbalance for selected @entity5 predisposition genes in @entity1 referred for routine diagnostic array comparative genomic hybridisation (CGH). DESIGN: Audit of findings from application of array CGH for @entity1 referred for @entity245 , @entity854 and @entity600 in 4805 @entity1 referred to Guy's and St Thomas' NHS Foundation Trust for cytogenetic investigation from South East London, Kent and East Sussex and other genetic centres across the UK. RESULTS: 29 of 4805 (0.6%) @entity1 examined by array CGH had genomic imbalance of <5 Mb involving @entity5 predisposition genes. Six @entity1 were referred for syndromes involving @entity5 predisposition genes; none of the other 23 @entity1 with array CGH findings in @entity5 predisposition genes had any symptoms/family history stated on their referral form suggestive for the respective syndrome. Twelve whole gene deletions, two partial deletions, 12 duplications, two partial duplications, and one mosaic duplication were observed. In 17/29 @entity1 (59%), inheritance could not be established, eight imbalances were de novo, and four inherited. CONCLUSIONS: This new technology raises the possibility of unexpected findings in @entity5 predisposition genes. Therefore, the possibility of such findings has to be addressed in pre-test and post-test counselling by genetically trained healthcare professionals. As many of these findings have not been described previously, their clinical significance is unknown and @entity1 need long-term follow-up to determine their clinical relevance. This will enable genetic healthcare professionals to advise such @entity1 about their @entity5 risks and appropriate @entity5 risk management options.
