title: Three novel BRCA1/BRCA2 mutations in breast/ovarian cancer families in Croatia.
abstract: BRCA1 and BRCA2 genes from 167 candidates (145 families) were scanned for mutations. We identified 14 pathogenic point mutations in 17 candidates, 9 in BRCA1 and 5 in BRCA2. Of those, 11 have been previously described and 3 were novel (c.5335C>T in BRCA1 and c.4139_4140dupTT and c.8175G>A in BRCA2). No large deletions or duplications involving BRCA1 and BRCA2 genes were identified. No founder mutations were detected for the Croatian population. Croatia shares most of the mutations with neighboring Slovenia and also with Germany, Austria and Poland. Two common sequence variants in BRCA1, c.2077G>A and c.4956G>A, were found more frequently in mutation carriers compared to healthy controls. No difference in BRCA2 variants was detected between the groups. Haplotype inference showed no difference in haplotype distributions between deleterious mutation carriers and non-carriers in neither BRCA1 nor BRCA2. In silico analyses identified one BRCA1 sequence variant (c.4039A>G) and two BRCA2 variants (c.5986G>A and c.6884G>C) as harmful with high probability, and inconclusive results were obtained for our novel BRCA2 variant c.3864_3866delTAA. Combination of QMPSF and HRMA methods provides high detection rate and complete coverage of BRCA1/2 genes. Benefit of BRCA1/2 mutation testing is clear, since we detected mutations in young unaffected women, who will be closely monitored for breast and ovarian cancer.
authors.affiliation: Laboratory for Hereditary Cancer, Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia. levanat@irb.hr
authors.forename: Sonja
authors.initials: S
authors.lastname: Levanat
authors.forename: Vesna
authors.initials: V
authors.lastname: Musani
authors.forename: Mirela Levacic
authors.initials: ML
authors.lastname: Cvok
authors.forename: Ilona
authors.initials: I
authors.lastname: Susac
authors.forename: Maja
authors.initials: M
authors.lastname: Sabol
authors.forename: Petar
authors.initials: P
authors.lastname: Ozretic
authors.forename: Diana
authors.initials: D
authors.lastname: Car
authors.forename: Domagoj
authors.initials: D
authors.lastname: Eljuga
authors.forename: Ljerka
authors.initials: L
authors.lastname: Eljuga
authors.forename: Damir
authors.initials: D
authors.lastname: Eljuga
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics*; D017523:Croatia; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods