Paternal UPD14 with sSMC derived from chromosome 14 in Kagami-Ogata syndrome

Abstract

Abstract Uniparental disomy (UPD) has been associated with several well-characterized disorders due to abnormal imprinting of the underlying genes. Depending on the parent-of-origin, paternal and maternal UPD are frequently associated with clinically distinct imprinting disorders. Here we report a neonatal case that was referred to Greenwood Genetic Center for clinical genetic testing. Prenatal ultrasound identified polyhydramnios and congenital cardiac anomalies and neonatal examination revealed a prune-like belly and bowel obstruction. Taking advantage of a variety of cytogenetic and molecular genetic approaches, we identified the presence of a small supernumerary marker chromosome (sSMC) associated with a complex chromosomal rearrangement derived from 14q11.2 and absence of heterozygosity on the chromosome 14q, indicative of uniparental isodisomy for chromosome 14. In addition, microsatellite DNA analysis of chromosome 14 showed UPD14 in this patient is paternal in origin, which is consistent with a clinical diagnosis of Kagami-Ogata syndrome (KOS). To our knowledge, this is the first case report of KOS resulting from paternal UPD14 and presence of sSMC with complex chromosomal rearrangement involving 14q11.2 without evidence of mosaicism.