First Report of Uniparental Isodisomy of Chromosome 15 Revealing Angelman Syndrome and Microphthalmia Associated With a Novel Homozygous ALDH1A3 Variant

ABSTRACT Paternal isodisomy of chromosome 15 (iUPD15) is a recognized cause of Angelman syndrome (AS), accounting for approximately 2%–5% of cases. Additionally, another recognized consequence of iUPD is the unmasking of autosomal recessive disorders. However, reports of recessive disorders resulting from iUPD15 remain scarce in the literature. Here, we report a Brazilian male patient with paternal iUPD15 who presented with clinical features consistent with AS and bilateral microphthalmia, the latter attributable to a novel homozygous likely pathogenic variant in ALDH1A3 (NM_000693.4:c.3G>A:p.(Met1?)) unmasked by the isodisomy. Comprehensive molecular investigation, including chromosomal microarray, microsatellite marker analysis, and whole exome sequencing, was essential to elucidate this diagnosis. To the best of our knowledge, this is the first case reported of Angelman syndrome and ALDH1A3 ‐related microphthalmia due to paternal iUPD15. This case highlights the importance of considering UPD in the context of imprinting disorders as well as a mechanism for unveiling recessive diseases.