Single Nucleotide Polymorphism array analysis for fetuses from balanced translocation carriers at the second trimester

Prenatal diagnosis is crucial for pregnancies from couples with a carrier of a balanced translocation. We retrospectively reviewed 195 pregnancies from 189 couples with a balanced translocation carrier. Of these, 126 were from natural conception, while 69 were conceived through assisted reproductive technology (ART) with preimplantation genetic diagnosis (PGD). Both single nucleotide polymorphism (SNP) array analysis and conventional karyotyping were conducted on all pregnancies, and karyotype-visible imbalances and pathogenic/likely pathogenic copy number variations (CNVs) were categorized as clinically significant abnormalities. In natural conception group, couples with a female carrier experiencing more than two miscarriages accounted for 30.2 %, significantly higher than the 14.0 % in male carrier couples (p < 0.05). In the PGD group, similar difference was observed between female and male carrier couples (p < 0.05). In the natural pregnancies, SNP array analysis yielded additional 12 cases of CNVs, including two cases of pathogenic (P)/likely pathogenic (LP) aberrations, four variants with uncertain significance (VUS), and six likely benign variants. Only two CNVs were found to be associated with translocation breakpoints, which were finally confirmed to be of parental inheritance. In the PGD pregnancies, two cases of VUS unrelated to the translocation breakpoints were revealed. Taken together, repeated miscarriage was more frequently observed in couples where the carrier was female than male. Conventional SNP array analysis in prenatal diagnosis indicated insufficient evidence to support the notion that balanced translocations increase the likelihood of fetuses having clinically significant CNVs.