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.

Duplication 12p and Pallister–Killian syndrome: A case report and review of the literature toward defining a Pallister–Killian syndrome minimal critical region

“…Ages of the patients described in the previously published case reports ranged from birth to 34 years. We also identified three reports of individuals with partial tetrasomy 12p [Dufke et al, 2001; Vermeesch et al, 2005; Huang et al, 2007]. Duplication sizes ranged from the entire short arm to microduplications of about 10 Mb, many of which are associated with characteristic traits of PKS (Table I).…”

“…With the aim of narrowing down the candidate chromosomal region for PKS, we reviewed the literatures of partial tetrasomy 12p as well. The reports with partial tetrasomy of 12p are limited to only three cases to date [Dufke et al, 2001; Vermeesch et al, 2005; Huang et al, 2007]. Vermeesch et al [2005] reported a patient with partial tetrasomy 12p of the smallest size (12p13.31–pter), although the authors concluded that the patient only had a partial PKS phenotype, given the lack of typical facial features, seizure, hearing loss, and skin pigmentation [Vermeesch et al, 2005].…”

Mosaic Intrachromosomal Triplication of (12)(p11.2p13) in a Patient with Pallister-Killian Syndrome

“…Powis et al [9] speculated that triplication of chromosome 12p could have arisen from telomere to telomere fusion of supernumerary analphoid isochromosome 12p with a normal chromosome 12. Indeed, there are three reports about PKS patients with analphoid inverted duplicated supernumerary marker chromosomes consisting of chromosome 12p [4,17–18]. …”

Supernumerary Ring Chromosome: An Etiology for Pallister-Killian Syndrome?

“…Although the most frequent abnormality is a supernumerary isochromosome of the short arm of chromosome 12, different variants have been reported such as coexisting trisomy 12p and tetrasomy 12p [8], ring of tetrasomy 12p [9] and an inverted duplicated 12p with a neocentromere [10]. …”