Mosaicism for Genome Wide Homozygosity Identified as an Incidental Finding in Two Apparently Healthy Pregnant Women.

Abstract

Uniparental Disomy (UPD) occurs when both copies of a chromosome or chromosomal segment originate from only one parent. Mosaic genome-wide UPD (mos gwUPD) is typically identified in cases of fetal demise and placental dysplasia or in prenatal cases, where imprinting effects are associated with abnormal ultrasound findings. Children with mos gwUPD and clinical features due to UPD-associated imprinting effects (especially Beckwith-Wiedemann syndrome) have been reported; however, reports of adults with mos gwUPD are rare. Here we describe mos gwUPD in two apparently healthy pregnant adult women. Carrier testing noted variants with skewed allelic ratios outside of the normal heterozygous range, prompting further testing. Single nucleotide polymorphism (SNP) microarray identified mosaicism for gwUPD in both individuals, present at 85% and 90%, respectively, in blood, with varying percentages in other tissues. Neither woman displayed clinical features that would be expected with gwUPD at the time of testing, although retrospective careful personal history was consistent. Both women had uneventful pregnancies and delivered full-term healthy infants. These two cases demonstrate that mos gwUPD can be an incidental finding identified in apparently healthy adult women. Clinical follow-up is important for tumor monitoring, genetic counseling, and monitoring of future pregnancies due to mos gwUPD in the maternal endometrial tissue.