The Molecular Detection of Germline Mutations in the BRCA1 and BRCA2 Genes Associated with Breast and Ovarian Cancer in a Romanian Cohort of 616 Patients.

The objective of this study was to identify and classify the spectrum of mutations found in the BRCA1 and BRCA2 genes associated with breast and ovarian cancer in female patients in Romania. Germline BRCA1 and BRCA2 mutations were investigated in a cohort of 616 female patients using NGS and/or MLPA methods followed by software-based data analysis and classification according to international guidelines. Out of the 616 female patients included in this study, we found that 482 patients (78.2%) did not have any mutation present in the two genes investigated; 69 patients (11.2%) had a BRCA1 mutation, 34 (5.5%) had a BRCA2 mutation, and 31 (5%) presented different type of mutations with uncertain clinical significance, moderate risk or a large mutation in the BRCA1 gene. Our investigation indicates the most common mutations in the BRCA1 and BRCA2 genes, associated with breast and ovarian cancer in the Romanian population. Our results also bring more data in support of the frequency of the c.5266 mutation in the BRCA1 gene, acknowledged in the literature as a founder mutation in Eastern Europe. We consider that the results of our study will provide necessary data regarding BRCA1 and BRCA2 mutations that would help to create a genetic database for the Romanian population.

Impact of genetic testing and family health history of cystic fibrosis in the early prenatal diagnosis and prevention of a new case of genetic disorder.

Cystic fibrosis (CF) is a multi-system autosomal recessive disorder, results of mutations in the CF transmembrane conductance regulator (CFTR) gene, located on the long arm of chromosome 7. We present a special family couple with particular medical history of CF, who comes to our Clinic for genetic tests and a prenatal genetic counseling, to prevent the birth of a new affected CF child. Genetic analysis showed that the first affected child, a daughter, is compound heterozygous for two clinically significant recessive mutations: c.1521_1523delCTT; p.Phe508del, inherited from her mother, who carries the same CFTR mutation, and c.1853_1863delTTTTGCATGAA; p.IIe618Argfs 2, inherited from her father, who is heterozygous, healthy carrier, for the same CFTR mutation. In our case report, early prenatal genetic testing, pre- and post-test genetic counseling was crucial in the management of the present pregnancy, to prevent the birth of a new affected CF child.