Xuan Chao, Wang Bin-Bin, Gao Ge, Bai Xiao-Yan, Yang Qin, Liu Xiao-Cheng, Jing Wen-Bin, Ma Xu, He Guo-Wei
TEDA International Cardiovascular Hospital, Medical College, Nankai University, Tianjin, PR China.
Genet Test Mol Biomarkers. 2012 Aug;16(8):984-7. doi: 10.1089/gtmb.2012.0003. Epub 2012 Jul 11.
Ventricular septal defect (VSD) is the most common congenital heart disease (CHD). A number of genetic studies have linked the gene of PLAGL1 to the etiology of CHD. The present study aimed to identify potential pathogenic mutations for PLAGL1 and to provide insights into the etiology of isolated VSD.
Case-control mutational analysis was performed in 300 patients with isolated VSD and 300 healthy controls. Two protein-coding extons of PLAGL1 and their partial flanking intron sequences were amplified by polymerase chain reaction and sequenced on an ABI3730 Automated Sequencer. CLC workbench software was used to compare the conservatism of PLAGL1 protein with other multiple species.
Neither missense nor frame-shift mutations were detected in two protein-coding extons of PLAGL1. But a novel synonymous variation (c.486A>G, p. E162E) was detected in protein-coding exon-2. The glutamic that translated with the mutational codon is conservative when compared with other species.
We detected a synonymous variation in the protein-coding exon-2 of PLAGL1 in isolated VSD patients. It is possible that the etiology of isolated VSD might not be directly linked with this mutation, but might be associated with other patterns of gene expression regulation in PLAGL1, such as in the methylation-dependent manner.
室间隔缺损（VSD）是最常见的先天性心脏病（CHD）。多项遗传学研究已将PLAGL1基因与CHD的病因联系起来。本研究旨在鉴定PLAGL1的潜在致病突变，并深入了解孤立性VSD的病因。
对300例孤立性VSD患者和300例健康对照进行病例对照突变分析。通过聚合酶链反应扩增PLAGL1的两个蛋白质编码外显子及其部分侧翼内含子序列，并在ABI3730自动测序仪上进行测序。使用CLC工作台软件比较PLAGL1蛋白与其他多个物种的保守性。
在PLAGL1的两个蛋白质编码外显子中均未检测到错义突变或移码突变。但在蛋白质编码外显子2中检测到一个新的同义变异（c.486A>G，p.E162E）。与其他物种相比，由突变密码子翻译的谷氨酸是保守的。
我们在孤立性VSD患者的PLAGL1蛋白质编码外显子2中检测到一个同义变异。孤立性VSD的病因可能与该突变没有直接联系，但可能与PLAGL1中其他基因表达调控模式有关，如甲基化依赖方式。
