We report the prenatal diagnosis of an unbalanced translocation between chromosome Y and chromosome 15 in a female fetus. Cytogenetic analysis of parental chromosomes revealed that the mother had a normal 46,XX karyotype, whereas the father exhibited a 46,XY,der(15)t(Y;15) karyotype. We performed cytogenetic analysis of the father's family as a result of the father and confirmed the same karyotype in his mother and brother. Fluorescence in situ hybridization and quantitative fluorescent-polymerase chain reaction analysis identified the breakpoint and demonstrated the absence of the SRY gene in female members. Thus, the proband inherited this translocation from the father and grandmother. This makes the prediction of the fetal phenotype possible through assessing the grandmother. Therefore, we suggest that conventional cytogenetic and molecular cytogenetic methods, in combination with family history, provide informative results for prenatal diagnosis and prenatal genetic counseling.
Chromosomes, Human, Pair 15* ; Cytogenetic Analysis ; Cytogenetics ; Fathers ; Female* ; Fetus* ; Fluorescence ; Genes, sry ; Genetic Counseling ; Grandparents ; Humans ; In Situ Hybridization ; Karyotype ; Mothers ; Parents ; Phenotype ; Prenatal Diagnosis* ; Sex Chromosome Aberrations ; Siblings

Objective: Familial cancer appears at a young age and its incidence is increasing. About 12% of familial ovarian cancer cases are associated with BRCA1/2 mutations (BRCAm). In this study, we investigated BRCA1 methylation may predict ovarian cancer in those with a family history of cancer (FHC) but without BRCA1/2 mutations (BRCAwt). Methods: Using peripheral blood DNA from 55 subjects without a history of cancer [cancer(−)] and 52 ovarian cancer patients, we examined BRCA1 promoter methylation through bisulfite sequencing of the promoter and expressed the results as the cumulative methylation index. Then, we evaluated the BRCA1 promoter methylation according to BRCA1/2 germline mutations. Results: BRCA1 methylation was more prevalent in the BRCAm cancer(−) group than in the BRCAwt cancer(−) group and ovarian cancer patients (p=0.031 and p=0.019, respectively). In the BRCAwt cancer(−) group, BRCA1 methylation was more prevalent in those with an FHC than in those without one and in the BRCAm cancer(−) group with an FHC (p=0.001 and p<0.001, respectively). Conclusion Our data suggest a predictive role of BRCA1 methylation profile for ovarian cancer in those without a history of cancer but with an FHC. BRCA1 methylation has important implications for diagnostic and predictive testing of those with BRCAwt cancer(−) status with FHC.