Mosaic Genome-Wide uniparental disomy (GW-UPD): Heterogeneity of a rare disorder poses diagnostic and management challenges

Abstract

<h3>Background</h3> The mosaic GW-UPD phenotype is associated with extensive clinical heterogeneity, much of which is attributable to varying levels of tissue mosaicism, with the clinical utility of diagnostic testing still not well defined. <h3>Aim</h3> To characterise the clinical and molecular profile of a patient with mosaic GW-UPD. <h3>Methods</h3> Detailed clinical information relied on available hospital records. The cytogenetics work-up included routine karyotype analysis and HumanCytoSNP-12 (Illumina) microarray study. Standard MRC-Holland kits were used for MS-MLPA characterisation of epigenetic marks. <h3>Results</h3> Fetal compromise and maternal hypertension resulted in premature birth at 30.3 weeks. Intrauterine growth had been normal. Post-natal onset of abdominal distension and anaemia requiring transfusion prompted investigations, including Rh typing. Two cell lines, one positive and one negative for the Rh-D antigen were detected. SNP microarray analysis revealed mosaic GW-UPD, consistent with the diploid karyotype 46, XX. Epigenotype analysis revealed KCNQ1OT1 hypomethylation, indicating paternal UPD, and an unusual methylation profile at <i>H19</i>. <h3>Discussion</h3> The non-specific clinical features of our patient highlight the challenge associated with diagnosis of the mosaic GW-UPD phenotype. The diagnosis is important because of benefits arising from screening for associated embryonic tumours. Our case demonstrates the diagnostic and clinical utility of characterising the epigenetic profile associated with GW-UPD.