A deep intronic recurrent CHEK2 variant c.1009-118_1009-87delinsC affects pre-mRNA splicing and contributes to hereditary breast cancer predisposition.

Germline CHEK2 pathogenic variants confer an increased risk of female breast cancer (FBC). Here we describe a recurrent germline intronic variant c.1009-118_1009-87delinsC, which showed a splice acceptor shift in RNA analysis, introducing a premature stop codon (p.

Contribution of Massive Parallel Sequencing to Diagnosis of Hereditary Ovarian Cancer in the Czech Republic.

Background: Ovarian cancer is a disease with high mortality. Approximately 1,000 women are diagnosed with ovarian cancer in the Czech Republic annually. Women harboring a mutation in cancer-predisposing genes face an increased risk of tumor development.

Germline CHEK2 Gene Mutations in Hereditary Breast Cancer Predisposition - Mutation Types and their Biological and Clinical Relevance.

Background: Hereditary mutations in the CHEK2 gene (which encodes CHK2 kinase) contribute to a moderately increased risk of breast cancer (BC) and other cancers. Large variations in the frequency of CHEK2 mutations and the occurrence of variants of unknown clinical significance (VUS) complicate estimation of cancer risk in carriers of germline CHEK2 mutations.

Patients And Methods: We performed mutation analysis of 1,526 high-risk Czech BC patients and 3,360 Czech controls.

Identification of deleterious germline CHEK2 mutations and their association with breast and ovarian cancer.

Germline mutations in checkpoint kinase 2 (CHEK2), a multiple cancer-predisposing gene, increase breast cancer (BC) risk; however, risk estimates differ substantially in published studies. We analyzed germline CHEK2 variants in 1,928 high-risk Czech breast/ovarian cancer (BC/OC) patients and 3,360 population-matched controls (PMCs). For a functional classification of VUS, we developed a complementation assay in human nontransformed RPE1-CHEK2-knockout cells quantifying CHK2-specific phosphorylation of endogenous protein KAP1.

Long-term significant seasonal differences in the numbers of new-borns with an orofacial cleft in the Czech Republic - a retrospective study.

Background: Choosing the optimal season for conception is a part of family planning since it can positively influence the pregnancy outcome. Changes in the monthly number of infants born with a birth defect can signal prenatal damage - death or malformation - related to a harmful seasonal factor. The aim of our paper was to search for possible seasonal differences in the numbers of new-borns with an orofacial cleft and thus for a period of conception that can increase the risk of orofacial cleft development.