title: Identification of a novel mutations BRCA1*c.80 + 3del4 and BRCA2*c.6589delA in Slovak HBOC families.
abstract: Mutations in the BRCA1 and BRCA2 genes account for the majority of hereditary breast ovarian cancer (HBOC) cases. However, after BRCA1 and BRCA2 screening still the most HBOC cases remain negative for any mutational event. Accordingly, in these cases raises the relevance to analyze the unusual BRCA1/2 variants of uncertain clinical significance. Complex RNA/cDNA analysis may constitute the solution and help to interpret the HBOC syndrome in the family. In our study we analyzed the novel, to our knowledge, not yet published mutations identified in Slovak HBOC families, c.80 + 3del4 (IVS2 + 3delAGTC) in BRCA1 gene and mutation c.6589delA (6817delA) in BRCA2 gene. To determine the effect of the BRCA1 mutation, we applied different approaches: segregation analysis of mutation with disease, presence in the set of unaffected controls and finally RNA/cDNA BRCA1 analysis. Novel BRCA2 mutation was determined performing direct sequencing analysis. In conclusion, considering the results from all used techniques we approved the mentioned mutations as seriously pathogenic and disease causing with clear effect on the onset of HBOC syndrome.
authors.affiliation: Department of Clinical Genetics, St. Elizabeth Cancer Institute, Bratislava, Slovakia. mkonecny@ousa.sk
authors.forename: Michal
authors.initials: M
authors.lastname: Konecny
authors.forename: Miriam
authors.initials: M
authors.lastname: Vizvaryova
authors.forename: Katarina
authors.initials: K
authors.lastname: Zavodna
authors.forename: Regina
authors.initials: R
authors.lastname: Behulova
authors.forename: Maria
authors.initials: M
authors.lastname: Gerykova Bujalkova
authors.forename: Tomas
authors.initials: T
authors.lastname: Krivulcik
authors.forename: Frantisek
authors.initials: F
authors.lastname: Cisarik
authors.forename: Juraj
authors.initials: J
authors.lastname: Kausitz
authors.forename: Eva
authors.initials: E
authors.lastname: Weismanova
mesh_terms: D000368:Aged; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005192:Family Health; D005260:Female; D017353:Gene Deletion; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D010375:Pedigree; D018154:Slovakia