Department of Pediatric Cardiology, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200127, China.
BMC Med Genet. 2011 Dec 21;12:169. doi: 10.1186/1471-2350-12-169.
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.
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.
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).
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.
患有 22q11.2 缺失综合征的患者中，75%-85%存在圆锥动脉干畸形（CTD）。迄今为止，尚未发现与 22q11.2 缺失一致相关的一致表型。遗传研究表明 TBX1 是该综合征发病机制的关键基因。本研究旨在确定 22q11.2 缺失在中国 CTD 患者中的发生率，以及 CTD 发病机制的可能机制。
我们纳入了 212 例 CTD 患者和 139 名无关的健康对照者。对所有 CTD 患者进行核型分析和多重连接依赖性探针扩增，对存在遗传缺失的患者及其亲属进行荧光原位杂交。对所有患者和健康对照者进行 TBX1 基因测序。统计分析采用 χ2 检验和 Fisher 确切概率法。
212 例 CTD 患者中发现 13 例（6.13%）患有 22q11.2 缺失综合征。13 例中，11 例为 CLTCL1 至 LZTR1 杂合性片段缺失；1 例为 CLTCL1 至 DRCR8 局灶性缺失；1 例为 CDC45L 至 LZTR1 局灶性缺失。22q11 缺失的 CTD 患者中，TBX1 基因的单倍体中存在 8 个序列变异。在 22q11 缺失患者中，一种单核苷酸多态性（SNP）的频率与非缺失患者不同（P<0.05），另外两种 SNP 在非缺失 CTD 患者和对照组之间的频率也不同（P<0.05）。
CTD，尤其是肺动脉闭锁伴室间隔缺损和法洛四联症，是与 22q11.2 缺失综合征最相关的最常见疾病。同时患有 CTD 和 22q11.2 缺失的患者，TBX1 基因通常存在典型或非典型缺失区域。我们的结果表明，TBX1 基因突变可能与 CTD 有关。
