Using Array-Based Comparative Genomic Hybridization to Diagnose Pallister-Killian Syndrome

Abstract

Pallister-Killian syndrome (PKS) is a rare multisystem disorder characterized by isochromosome 12p and tissue-limited mosaic tetrasomy 12p. In this study, we diagnosed three pediatric patients who were suspicious of having PKS using array-based comparative genomic hybridization (array CGH) and FISH analyses performed on peripheral lymphocytes. Patients 1 and 2 presented with craniofacial dysmorphic features, hypotonia, and a developmental delay. Array CGH revealed two to three copies of 12p in patient 1 and three copies in patient 2. FISH analysis showed trisomy or tetrasomy 12p. Patient 3, who had clinical features comparable to those of patients 1 and 2, was diagnosed by using FISH analysis alone. Here, we report three patients with mosaic tetrasomy 12p. There have been only reported cases diagnosed by chromosome analysis and FISH analysis on skin fibroblast or amniotic fluid. To our knowledge, patient 1 was the first case diagnosed by using array CGH performed on peripheral lymphocytes in Korea.

Keywords: Array CGH; Isochromosome 12p; Pallister-Killian syndrome; Tetrasomy 12p.

Fig. 1. Genomic analysis. (A) Array CGH analysis of chromosome 12 performed on DNA from blood lymphocytes. Log 2 ratio data are presented according to the position in the human genome (NCBI build 37/hg19). Patient 1 showed two to three copies of 12p13.33-p11.21 (arr 12p13.33p11.21×2-3). Patient 2 had a duplication of the entire short arm of chromosome 12, 12p13.3-p11.1 (arr 12p13.3p11.1×3). (B) FISH results from three patients. FISH analysis revealed four copies in addition to the three copies of TEL (green) on 12p13 in patient 1 and four copies of TEL (green) on 12p13 in patients 2 and 3. The red signal indicates AML1 (21q22).