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

Abstract

Abstract Background It is widely recognized that prenatal diagnosis should be offered to pregnancies from couples with a carrier of a balanced translocation. This study aimed to assess the utility of single nucleotide polymorphism array (SNP array) for pregnancies involving at least one parent with a balanced translocation during the second trimester. Material and methods This retrospective study analyzed prenatal diagnosis data from 195 consecutive pregnancies involving couples with a balanced translocation carrier. Of these, 69 pregnancies were conceived through assisted reproductive technology (ART) with preimplantation genetic diagnosis (PGD), while 126 were natural pregnancies. The cohort consisted of 33 couples with Robertsonian translocation carriers and 155 couples with reciprocal translocation carriers. Both SNP array analysis and conventional karyotyping were conducted on all cases, categorizing karyotype-visible imbalances and pathogenic/likely pathogenic copy number variants (CNVs) as clinically significant abnormalities. Results Among cases involving natural conception, the rate of cases experiencing more than two early miscarriages in Robertsonian translocation couples was significantly lower than that in Reciprocal translocation couples (5.0% vs. 26.0%, p < 0.05). In couples with female carrier, cases experiencing more than two early miscarriages accounted for 30.2%, significantly higher than the 14.0% in male carrier couples (p < 0.05). A total of 7 (5.6%) cases of unbalanced translocation pregnancies were identified in natural conception pregnancies. Compared with karyotyping, an additional 12 cases of copy number variants (CNVs) were revealed by SNP array analysis, including 2 (1.0%) cases of pathogenic (P) /likely pathogenic (LP) aberrations, 4 (2.0%) variants with uncertain significance (VOUS), and 6 (3.0%) likely benign variants. Both of the clinically significant CNVs were detected in fetuses with a balanced translocation but were unrelated to the translocation breakpoints. Two cases with breakpoints-related CNVs were confirmed to be of parental inheritance and considered likely benign. In fetuses with ultrasound anomalies, the incidence of clinically significant findings was 33.3%, significantly higher than the 1.7% in fetuses with normal ultrasonography (p < 0.05). Conclusion Early miscarriage was more often observed in pregnancies from couples with female carrier and reciprocal translocation couples. Insufficient evidence indicates that balanced translocations increase the likelihood of clinically significant CNVs in the fetus, particularly those related to translocation breakpoints.