185delAG in a Sri Lankan family with no Ashkenazi ancestry. W. Meschino, H. Dorman, J. Furnival, J. Guo, J. Honeyford, D. Kennedy, M. Shama, J. Steer, K. Chun, D. Allingham-Hawkins. Genetics Program, North York General Hosp, Toronto, ON, Canada.
   A 42 year old Sri Lankan woman presented to the familial breast/ovarian cancer clinic for counselling due to a history of invasive ductal carcinoma at age 37 followed by endometrial cancer at age 41. Family history revealed that her mother had developed breast cancer at age 37 and died of cancer at age 42. There were no other known cases of breast or ovarian cancer in the family. Screening of the BRCA1 and BRCA2 genes was performed using the protein truncation test plus direct sequencing of exons 2 and 5 of BRCA1. The common Ashkenazi Jewish (AJ) mutation, 185delAG, was found in exon 2 of BRCA1. A repeat analysis on a fresh specimen confirmed the finding. 185delAG is considered a "founder" mutation in the AJ population with a carrier frequency of ~1%. Carriers of 185delAG have a lifetime breast cancer risk of approximately 60%. Outside of the AJ population, however, this mutation is relatively rare. It has been observed in a group of non-Jewish Americans of Spanish descent from the San Luis Valley in Colorado as well as occasionally in other individual families with no known Jewish ancestry. This is the first report, to our knowledge, of 185delAG being identified in a Sri Lankan family. Haplotype analysis is pending to determine if the mutation is residing on the same haplotype as the common Ashkenazi mutation, another previously identified haplotype or one not previously described.
   This family also presented an unusual counselling challenge in that when the younger, unaffected sister of our patient presented for counselling and predictive testing, she requested that the test results be given not to her but to her older brother, who attended the counselling session with her, as he is the paternal figure in the family. The counsellor was assured that the woman herself would return for full counselling but only after her brother had received her results and gently conveyed them to her. This is an example of the importance of flexibility and sensitivity to cultural traditions while delivering genetic services.