Lee Curtis David, Bekheirnia Nasim, Potocki Lorraine, Matyakhina Ludmila, Bekheirnia Mir Reza
Baylor College of Medicine, Houston, Texas, USA.
Texas Children's Hospital, Houston, Texas, USA.
Case Rep Genet. 2025 Jul 25;2025:4973753. doi: 10.1155/crig/4973753. eCollection 2025.
Uniparental disomy (UPD) constitutes an unconventional mode of inheritance that disrupts the typical biparental genetic contribution and may result in phenotypic abnormalities. This report centers on a patient diagnosed with Bartter syndrome Type 1, attributed to a homozygous pathogenic variant in unmasked by mosaic paternal UPD of chromosome 15. We hypothesize that this pattern (or constellation) emerged from a trisomy rescue event, resulting in two distinct cell lines. Concurrently, the unmasking of a pathogenic paternal variant by trisomy rescue resulted in the manifestation of Bartter syndrome Type 1. The maternally derived ring chromosome 15 and its impact on nondisjunction and UPD elucidate a unique etiology of Bartter syndrome. Furthermore, the presence of a pathogenic paternal variant underscores the pivotal role of trisomic rescue and paternal UPD in unveiling a recessive variant.
单亲二体（UPD）构成了一种非常规的遗传模式，它打破了典型的双亲基因贡献，可能导致表型异常。本报告聚焦于一名被诊断为1型巴特综合征的患者，其病因是15号染色体单亲二体掩盖了一个纯合致病变异。我们推测这种模式（或组合）源于三体挽救事件，导致了两种不同的细胞系。同时，三体挽救使致病父本变异得以暴露，导致了1型巴特综合征的表现。母源的15号环状染色体及其对不分离和UPD的影响阐明了巴特综合征的独特病因。此外，致病父本变异的存在强调了三体挽救和父本UPD在揭示隐性变异中的关键作用。
