R2034C in BRCA2


Description 

Arg2034>Cys 
6382C>T

Biochemical data 

Arg2034 is lying between the 6th and 7th internal repeat in BRCA2 (1).

Co-segregation with disease

R2034C has been reported only once in the Dutch BRCA1/2 mutation database so far. It was detected in male breast cancer family RUL023. A bilateral breast cancer patient (dx35, 41) and her cousin, a breast cancer patient diagnosed at age 33, were found to carry it. No DNA was available for the sister of the latter patient, who developed a uterus carcinoma at age 62. Haplotype analysis with flanking markers for BRCA2 indicated that her four children all segregated a haplotype which could be associated with the wildtype BRCA2 allele in her sisters and their children. It remains possible, therefore, that she carries the R2034C. The male breast cancer patient (dx76) and his sister, diagnosed with breast cancer at age 48, are obligate carriers.
Conclusion: R2034C shows perfect co-segregation with breast cancer in family RUL023. This family had a >75% prior probability of being due to a mutation in BRCA2 (2).

 

References

1. Bignell G, Micklem G, Stratton MR, Ashworth A, Wooster R (1997) The BRC repeats are conserved in mammalian BRCA2 proteins. Hum Mol Genet, 6: 53-58.

2. Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P, Bishop DT, Weber B, Lenoir G, Chang-Claude J, Sobol H, Teare MD, Struewing J, Arason A, Scherneck S, Peto J, Rebbeck TR, Tonin P, Neuhausen S, Barkardottir R, Eyfjord J, Lynch H, Ponder BA, Gayther SA, Birch JM, Lindblom A, Stoppa-Lyonnet D, Bignon Y, Borg A, Hamann U, Haites N, Scott RJ, Maugard CM, Vasen H, Seitz S, Cannon-Albright LA, Schofield A, Zelada-Hedman M, Breast Cancer Linkage Consortium (1998) Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. Am J Hum Genet, 62: 676-689.


Last update: 19-03-2002