Large regions of homozygosity in prenatal diagnosis

Abstract Chromosomal microarrays (CMA) incorporate single nucleotide polymorphisms to enable the detection of regions of homozygosity (ROH). Here, we retrospectively analyzed 6288 prenatal cases who performed CMA to explored the clinical implications of large ROH in prenatal diagnosis. We analyzed cases with ROH larger than 10 megabases and reviewed the ultrasound findings; karyotype results and pregnancy follow‐up data. Cases with possible imprinting disorders were assessed by methylation‐specific multiplex ligation‐dependent probe amplification. In total, we identified 50 cases with large ROH and chromosomes 1 and 2 were the most affected. About 59.18% of the ROH cases had ultrasound abnormalities, with the most common findings being ultrasound soft‐marker abnormalities. There were seven fetuses had ROH which covered almost the entire chromosome and four had terminal ROH that involved almost the entire long arm of the chromosomes, which indicated uniparental disomy (UPD), of which 70% showed abnormal ultrasound findings. Ten cases with multiple ROH on different chromosomes indicated the third to fifth degree of consanguinity. In this study, we highlighted the clinical relevance of large ROH related to UPD. The analysis of ROH allowed us to gain further understanding of complex cytogenetic and disease mechanisms in prenatal diagnosis.