Pallister–Killian syndrome: tetrasomy of 12pter→12p11.22 in a boy with an analphoid, inverted duplicated marker chromosome

Abstract

Supernumerary marker chromosomes (SMCs) without detectable alphoid DNA are predicted to have a neocentromere and have been referred to as mitotically stable neocentromere marker chromosomes (NMCs). Here we report the molecular cytogenetic characterization of a new case of Pallister-Killian syndrome (PKS) in a boy with an analphoid, inverted duplicated NMC derived from 12pter-->12p11.22 in his fibroblasts by using high-resolution comparative genetic hybridization (HR-CGH), multiplex fluorescent in situ hybridization (FISH) and bacterial artificial chromosome (BAC)-FISH mapping analyses with various alpha-satellite DNA probes, subtelomere probes and BAC-DNA probes. Precise identification of SMCs and NMCs is of essential importance in genetic counseling. HR-CGH is a more informative and often a faster way of precisely identifying the origin of SMCs. This case is the third report of PKS with an NMC containing an inverted duplication of partial 12p with available clinical data. These observations may help to determine the critical region for PKS and the mechanisms leading to the origin of the NMC derived from 12pter-->12p11.22 - a region that appears to be susceptible to the formation of neocentromeres. The use of subtelomeric probe PCP12p in buccal cells appears superior to the use of the centromere probe D12Z3 for the diagnosis of the PKS.