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

• Main Authors: Xu Yue-Juan (Author), Wang Jian (Author), Xu Rang (Author), Zhao Peng-Jun (Author), Wang Xi-Ke (Author), Sun Heng-Juan (Author), Bao Li-Ming (Author), Shen Jie (Author), Fu Qi-Hua (Author), Li Fen (Author), Sun Kun (Author)
• Format: Book
• Published: BMC, 2011-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

<p>Abstract</p> <p>Background</p> <p>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 <it>TBX1 </it>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.</p> <p>Methods</p> <p>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 <it>in situ </it>hybridization was performed for the patients with genetic deletions and their relatives. The <it>TBX1 </it>gene was sequenced for all patients and healthy controls. The <it>χ</it>²and Fisher's exact test were used in the statistical analysis.</p> <p>Results</p> <p>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 <it>CLTCL1 </it>to <it>LZTR1</it>; one presented with a regional deletion from <it>CLTCL1 </it>to <it>DRCR8</it>; and one presented with a regional deletion from <it>CDC45L </it>to <it>LZTR1</it>. There were eight sequence variants in the haploid <it>TBX1 </it>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 (<it>P </it>< 0.05), and the frequencies of two other SNPs were different between the non-del CTDs patients and controls (<it>P </it>< 0.05).</p> <p>Conclusions</p> <p>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 <it>TBX1 </it>gene. Our results indicate that <it>TBX1 </it>genetic variants may be associated with CTDs.</p>

Item Description

10.1186/1471-2350-12-169
1471-2350