Large BRCA1 deletion in African Americans

• Published in: The FASEB journal 2007, Vol.21 (6), p.LB38-LB38
• Main Authors: Abdel‐Hameed, Enass, Beyene, Desta, Hill, Janell, Dunston, Georgia, Broome, Carolyn
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.21.6.LB38-c

Large genomic rearrangements have been observed in BRCA1 carriers and frequently involve recombination between intron Alu sequences, leading to a non‐functional protein. Multiplex ligation‐dependent probe amplification (MLPA) is a technique that can detect the change in copy number of the 24 exons of BRCA1 simultaneously in one reaction. A large deletion of exons 1a, 1b, and 2 has been detected in triplicate MLPA analyses of one (family #70) of our 55 high‐risk African American breast cancer families. The BRCA1 Pro871Leu polymorphism is usually in linkage disequilibrium with the BRCA1 β promoter C/G 1802 polymorphism. Linkage of the Pro871Leu polymorphism to the β promoter C/G 1802 polymorphism was tested using specific β promoter primers. In family #70, the Pro871Leu polymorphism was linked to a hemizygous/homozygous C in the β promoter. The hemizygosity of the BRCA1 β promoter 1802 polymorphism suggests that the deletion of exons 1a, 1b, and 2 extends into the promoter region. A 37 kb deletion has been reported in Caucasians that removes the BRCA1 promoter and BRCA1 introns 1a, 1b, and 2 resulting in no BRCA1 transcript. Due to the 98% identity of sequences in BRCA1 intron 2 and Ψ‐BRCA1 intron2, this region is a hot spot for recombination. This is the first report of a large deletion of exons 1a, 1b, and 2 in an African American family. Supported by U.S. Army grant DAMD17‐01‐1‐0266.