title: Strong founder effects in BRCA1 mutation carrier breast cancer patients from Latvia. Mutation in brief no. 258. Online.
abstract: Germ-line mutations of the BRCA1 gene account for approximately half of the cases of hereditary breast/ovarian cancers. We have screened index patients from 15 breast cancer families and 8 sporadic breast cancer patients from Latvia for mutations in all coding exons of the BRCA1 gene, using combined Heteroduplex Analysis/SSCP followed by direct sequencing of the variants. BRCA1 germ-line mutations proved to be frequent in Latvian breast cancer patients, also in moderate-risk families and sporadic patients. Out of 23 cases a total of 8 patients (35%) exhibited three different mutations (5382insC, C61G, 4153delA). Interestingly, these three recurrent mutations accounted for all mutations in our sample set and no unique mutation was found. The 5382insC and C61G mutations accounted for 63% (5/8) and 25% (2/8) of all mutations, respectively. Allelotyping suggested a common founder in each recurrent mutation. Additional one-hundred hospital-based incident breast cancer patients were screened for the three mutations and 4 other 5382insC mutation carriers were identified (4%). Patients with C61G and 4153delA mutations were all Latvians, whilst the majority of 5382insC carriers (7/9=78%) were of Russian ethnicity, which is intriguing for the supposed Baltic origin of this mutation.
authors.affiliation: National Institute of Oncology, Dept. Molecular Biology, Budapest, Hungary.
authors.forename: B
authors.initials: B
authors.lastname: Csokay
authors.forename: L
authors.initials: L
authors.lastname: Tihomirova
authors.forename: A
authors.initials: A
authors.lastname: Stengrevics
authors.forename: O
authors.initials: O
authors.lastname: Sinicka
authors.forename: E
authors.initials: E
authors.lastname: Olah
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D019398:Genes, BRCA1; D018095:Germ-Line Mutation; D020180:Heteroduplex Analysis; D006579:Heterozygote; D006801:Humans; D007844:Latvia; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational