Genome-wide androgenetic mosaicism

Individuals with mosaic paternal uniparental disomy (UPD) of apparently all chromosomes have recently been described. They show a 46,XX karyotype, but with a mixture of normal biparental cells and cells entirely of paternal isodisomic origin. We describe an infant who primarily showed signs of Beckwith-Wiedemann syndrome (BWS), but also had other severe and eventually lethal medical problems, notably refractory hypoglycemia. We performed methylation studies for BWS, but incidentally for Angelman syndrome (AS) on leukocytes and in a skin FFPE sample. We also performed chromosome microarray [CNV and single-nucleotide polymorphism (SNP) array] on leukocytes. We found that the patient had hypomethylation consistent with both BWS and AS. Remarkably, this was due to mosaic paternal UPD for chromosomes 11 and 15, respectively. The SNP microarray showed mosaic paternal UPD for all chromosomes. Patients with unusual phenotypes for a typical imprinting disorder should be studied further with assays for imprinted loci on other chromosomes. Chromosomal SNP microarrays are useful in identifying patients with multiple UPDs, sometimes of the whole genome.