Prenatal diagnosis of large regions of homozygosity (ROH) in non-imprinted areas.

Objective

The aim of the present study was to analyze prenatal diagnostic indications, diagnostic results, and pregnancy outcomes associated with fetuses exhibiting large regions of homozygosity (ROH) in non-imprinted regions, ultimately providing a reference for related prenatal diagnosis and genetic counseling.

Methods

A retrospective review was conducted on cases of fetuses prenatally diagnosed with large ROH in non-imprinted regions at our center between January 2019 and December 2021. This review encompassed maternal age, prenatal ultrasound findings, non-invasive prenatal testing (NIPT) results, adverse pregnancy histories, parental karyotype, and the results of prenatal diagnosis, which included karyotype analysis and chromosomal microarray (CMA) testing. Furthermore, pregnancy outcomes and postnatal phenotypes were also assessed.

Results

Among the 14 reviewed cases, one presented with a structural ultrasound abnormality, and five exhibited isolated ultrasound soft markers. Six patients underwent NIPT, and their results correlated with the prenatal diagnosis outcomes. CMA testing detected whole-chromosome ROH in two cases and ROH segments in 12 cases, whereas karyotype analysis for all 14 cases yielded normal results. Of these 14 cases, one ended in miscarriage, one in induction of labor, and 12 resulted in normal phenotypic presentation at birth. Follow-up evaluations conducted 4-6 years postpartum confirmed the absence of phenotypic abnormalities in nine cases.

Conclusion

NIPT demonstrates potential for identifying ROH. Cases with large ROH in non-imprinted regions often show prenatal ultrasound soft markers but no postnatal phenotypes. Genetic counseling for ROH cases is complex, necessitating the consideration of recessive genetic disorders, uniparental disomy (UPD) in imprinted regions, mosaicism, and the reproductive risks and ethical implications associated with parental consanguinity.