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Effect of <it>BRCA2 </it>sequence variants predicted to disrupt exonic splice enhancers on <it>BRCA2 </it>transcripts

By Brewster Brooke L, Pettigrew Christopher A, Whiley Phillip J, Walker Logan C, Spurdle Amanda B and Brown Melissa A


<p>Abstract</p> <p>Background</p> <p>Genetic screening of breast cancer patients and their families have identified a number of variants of unknown clinical significance in the breast cancer susceptibility genes, <it>BRCA1 </it>and <it>BRCA2</it>. Evaluation of such unclassified variants may be assisted by web-based bioinformatic prediction tools, although accurate prediction of aberrant splicing by unclassified variants affecting exonic splice enhancers (ESEs) remains a challenge.</p> <p>Methods</p> <p>This study used a combination of RT-PCR analysis and splicing reporter minigene assays to assess five unclassified variants in the <it>BRCA2 </it>gene that we had previously predicted to disrupt an ESE using bioinformatic approaches.</p> <p>Results</p> <p>Analysis of <it>BRCA2 </it>c.8308 G > A (p.Ala2770Thr) by mRNA analysis, and <it>BRCA2 </it>c.8962A > G (p.Ser2988Gly), <it>BRCA2 </it>c.8972G > A (p.Arg2991His), <it>BRCA2 </it>c.9172A > G (p.Ser3058Gly), and <it>BRCA2 </it>c.9213G > T (p.Glu3071Asp) by a minigene assay, revealed no evidence for aberrant splicing.</p> <p>Conclusions</p> <p>These results illustrate the need for improved methods for predicting functional ESEs and the potential consequences of sequence variants contained therein.</p

Topics: Medicine (General), R5-920, Medicine, R, DOAJ:Medicine (General), DOAJ:Health Sciences, Genetics, QH426-470, Biology (General), QH301-705.5, Science, Q, DOAJ:Genetics, DOAJ:Biology, DOAJ:Biology and Life Sciences, Internal medicine, RC31-1245
Publisher: BioMed Central
Year: 2010
DOI identifier: 10.1186/1471-2350-11-80
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