Haskell Gloria T, Askree S Hussain, Kline Laura, Hasadsri Linda, Cabral Huong, Gadi Inder, Schwartz Stuart
Labcorp, Cytogenetics, Labcorp, Durham, North Carolina, USA.
Labcorp Molecular Genetics, Labcorp, Atlanta, Georgia, USA.
Am J Med Genet A. 2025 Sep;197(9):e64106. doi: 10.1002/ajmg.a.64106. Epub 2025 Apr 30.
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.
单亲二体（UPD）是指一条染色体或染色体片段的两个拷贝均仅来自父母一方。全基因组嵌合单亲二体（mos gwUPD）通常在胎儿死亡和胎盘发育异常的病例中被发现，或在产前病例中被识别，这些病例中印记效应与异常超声检查结果相关。已有报道称患有mos gwUPD且具有与UPD相关印记效应导致的临床特征的儿童（尤其是贝克威思-维德曼综合征）；然而，关于成年mos gwUPD患者的报道却很少。在此，我们描述了两名看似健康的成年孕妇中的mos gwUPD情况。携带者检测发现等位基因比例偏斜且超出正常杂合范围的变异，从而促使进一步检测。单核苷酸多态性（SNP）微阵列在两名个体中均鉴定出全基因组嵌合单亲二体，在血液中的比例分别为85%和90%，在其他组织中的比例各不相同。尽管回顾性仔细询问个人病史是相符的，但两名女性在检测时均未表现出预期的全基因组嵌合单亲二体临床特征。两名女性均妊娠顺利并分娩出足月健康婴儿。这两例病例表明，mos gwUPD可能是在看似健康的成年女性中偶然发现的。由于母体子宫内膜组织中存在mos gwUPD，临床随访对于肿瘤监测、遗传咨询以及未来妊娠的监测非常重要。
