Identification of a novel mutations c.80 + 3del4 and *c.6589delA in Slovak HBOC families

Michal Konecny (1) , Miriam Vizvaryova (1) , Katarina Zavodna (1, 2) , Regina Behulova (3) , Maria Gerykova Bujalkova (2) , Tomas Krivulcik (2) , Frantisek Cisarik (4) , Juraj Kausitz (1) , Eva Weismanova (1)

1 Department of Clinical Genetics
2 Laboratory of Cancer Genetics
3 Institute of Medical Biology and Genetics, Faculty of Medicine
4 Department of Clinical Genetics

Mutations in the and genes account for the majority of hereditary breast ovarian cancer (HBOC) cases. However, after and screening still the most HBOC cases remain negative for any mutational event. Accordingly, in these cases raises the relevance to analyze the unusual 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 gene and mutation c.6589delA (6817delA) in gene. To determine the effect of the mutation, we applied different approaches: segregation analysis of mutation with disease, presence in the set of unaffected controls and finally RNA/cDNA analysis. Novel 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.

Mots clés: Novel mutation; Splicing mutation; Hereditary breast ovarian cancer (HBOC); Slovak population

Michal Konecny, Miriam Vizvaryova, Katarina Zavodna, Regina Behulova, Maria Gerykova Bujalkova, et al.. Identification of a novel mutations c.80 + 3del4 and *c.6589delA in Slovak HBOC families. Breast Cancer Research and Treatment, 2008, 119 (1), pp.233-237. ⟨10.1007/s10549-008-0244-6⟩. ⟨hal-00486602⟩