Cabral, Huong

ABSTRACTUniparental 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.

Abstract Uniparental disomy (UPD) is the inheritance of both chromosomal homologs from one parent. Depending on the chromosome involved and the parental origin, UPD may result in phenotypic abnormalities due to aberrant methylation patterns or unmasking recessive conditions in isodisomic regions. UPD primarily originates from somatic rescue of a single meiotically‐derived aneuploidy, most commonly a trisomy. Double UPD is exceedingly rare and triple UPD has not been previously described. Here, we report two unrelated clinical cases with UPD of multiple chromosomes; an 8‐month‐old male with maternal isodisomy of chromosome 7 and paternal isodisomy of chromosome 9, and a 4‐week‐old female with mixed paternal UPD for chromosomes 4, 10, and 14. These cases also demonstrate that although extremely rare, the detection of AOH on two or more chromosomes may warrant additional clinical and laboratory investigation such as methylation and STR marker analysis, especially when involving chromosomes known to be associated with imprinting disorders.