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Open Access Research article

Detecting 22q11.2 deletion in Chinese children with conotruncal heart defects and single nucleotide polymorphisms in the haploid TBX1 locus

Yue-Juan Xu1, Jian Wang2, Rang Xu3, Peng-Jun Zhao1, Xi-Ke Wang1, Heng-Juan Sun4, Li-Ming Bao45, Jie Shen6, Qi-Hua Fu2, Fen Li1 and Kun Sun17*

Author Affiliations

1 Department of Pediatric Cardiology, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200127, China

2 Medical Laboratory, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200127, China

3 Medical Laboratory, Scientific Research Center, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, China

4 Medical Laboratory, Shanghai Children's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200040, China

5 Division of Human Genetics, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA

6 Department of Pediatric Cardiology, Shanghai Children's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200040, China

7 Department of Pediatric Cardiology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, China

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BMC Medical Genetics 2011, 12:169  doi:10.1186/1471-2350-12-169

Published: 21 December 2011

Abstract

Background

Conotruncal heart defects (CTDs) are present in 75-85% of patients suffering from the 22q11.2 deletion syndrome. To date, no consistent phenotype has been consistently correlated with the 22q11.2 deletions. Genetic studies have implicated TBX1 as a critical gene in the pathogenesis of the syndrome. The aim of study was to determine the incidence of the 22q11.2 deletion in Chinese patients with CTDs and the possible mechanism for pathogenesis of CTDs.

Methods

We enrolled 212 patients with CTDs and 139 unrelated healthy controls. Both karyotypic analysis and multiplex ligation-dependent probe amplification were performed for all CTDs patients. Fluorescence in situ hybridization was performed for the patients with genetic deletions and their relatives. The TBX1 gene was sequenced for all patients and healthy controls. The χ2 and Fisher's exact test were used in the statistical analysis.

Results

Thirteen of the 212 patients with CTDs (6.13%) were found to have the 22q11.2 deletion syndrome. Of the 13 cases, 11 presented with a hemizygous interstitial microdeletion from CLTCL1 to LZTR1; one presented with a regional deletion from CLTCL1 to DRCR8; and one presented with a regional deletion from CDC45L to LZTR1. There were eight sequence variants in the haploid TBX1 genes of the del22q11 CTDs patients. The frequency of one single nucleotide polymorphism (SNP) in the del22q11 patients was different from that of the non-del patients (P < 0.05), and the frequencies of two other SNPs were different between the non-del CTDs patients and controls (P < 0.05).

Conclusions

CTDs, especially pulmonary atresia with ventricular septal defect and tetralogy of Fallot, are the most common disorders associated with the 22q11.2 deletion syndrome. Those patients with both CTDs and 22q11.2 deletion generally have a typical or atypical deletion region within the TBX1 gene. Our results indicate that TBX1 genetic variants may be associated with CTDs.