Two contiguously located germline BRCA1 mutations in a Spanish early-onset breast cancer family.

We identified two BRCA1 mutations in a high risk breast cancer family: the missense 1240 C > T (Thr > Ile) and the 1241delAC at codon 374, which results in a stop at codon 376. Both were contiguously located in the same BRCA1 gene, in a motif of 11 amino acids, which is highly conserved across human, canine and murine species. The presence of missense mutations in this motif in breast-cancer families suggests an important functional role for this protein region and a potential deleterious effect of the 1240C > T mutation.