Challenging diagnoses of tetraploidy/diploidy and trisomy 12: utility of first-tier prenatal testing methods

Introduction: Chromosome mosaicism and low-grade mosaicism present a challenge for diagnosis in the era of SNP array and NGS. Tetraploidy is a rare numerical chromosomal abnormality characterized by the presence of four copies of each chromosome. The prevalence of tetraploidy/diploidy mosaicism cases is extremely rare in the human population. Accurate estimates of the frequency of this chromosomal anomaly are lacking due to its classification as an extremely rare and difficult-to-detect condition.Methods: In this report, we describe two cases involving challenging diagnoses of tetraploidy/diploidy and trisomy 12. We utilized advanced genetic testing techniques, including SNP array, to examine the chromosomal abnormalities in these cases. We compared the results from SNP array to conventional G band karyotyping to assess the utility of first-tier prenatal testing methods.Results:Our analysis revealed two cases of tetraploidy/diploidy and trisomy 12 with atypical presentations. SNP array analysis provided higher resolution and more precise information about the chromosomal anomalies in these cases compared to conventional G band karyotyping. Additionally, the prevalence of tetraploidy/diploidy mosaicism was confirmed to be extremely rare in the population.Discussion: Low-level mosaicism is difficult to diagnose, and in many cases, it has traditionally been identified through techniques such as G band karyotype or FISH. Microarray has become an invaluable diagnostic tool for detecting chromosomal abnormalities, offering high-resolution insights. However, it may not always be able to detect rare occurrences of tetraploidy or tetraploidy/diploidy mosaicism. As a result, it is recommended to perform a G band karyotype analysis after obtaining a negative microarray result before considering other diagnostic methods with a potentially higher yield of diagnosis. For the detection of low-level mosaicism, combined diagnostic methods should be considered. The diagnosis of mosaicism is a multistep process that can be time-consuming, often requiring the application of more than one diagnostic technique. This approach is crucial for accurate diagnosis and comprehensive patient care. Further research is warranted to better understand the underlying mechanisms of these rare chromosomal anomalies and to develop more effective diagnostic strategies for challenging cases

Cystathionine β-synthase 844ins68 Genetic Polymorphism in Spontaneous Abortion Susceptibility

Aim: Genetic polymorphisms in homocysteine-related genes are subject of a large body of research in pregnancy and newborn associated pathologies. The enzyme cystationine β-synthase (CBS) is involved in the transsulfuration pathway of homocysteine to cysteine. Our objective was to analyze the association of a common polymorphism exhibited by the CBS gene, 844ins68, with idiopathic spontaneous abortions (SA). Material and Methods: 131 patients with a history of at least one unexplained SA and 135 healthy women with at least one successful pregnancy and no SA were included in a case-control study. Simplex PCR was used to genotype the cases and control volunteers for the CBS 844ins68 polymorphism. Fisher’s exact test was performed to obtain the odds-based parameters describing the relationship between the two variables. Results: The variant allele was encountered with a frequency of 0.08 in the SA group and 0.048 in controls. The dominant model analysis of risk revealed the OR 1.957, 95%CI [0.920, 4.162], Fisher’s p = 0.09. Conclusion: The findings suggest possible effects of this polymorphism in SA risk that did not reach the significance level in this study. Future studies might validate or clarify the association between CBS 844ins68 and idiopathic SA