中文摘要：

目的：研究先天性心脏病（congenital heart disease,CHD）相关HAND1基因新突变。方法：入选CHD患儿136例及健康对照儿童200名,抽提基因组DNA,通过聚合酶链反应测序筛查HAND1基因突变。应用计算机软件评估突变氨基酸的保守性并预测突变的致病性,应用双荧光素酶报告基因分析系统分析突变对HAND1功能的影响。结果：在1例法洛四联征患儿发现1种新的HAND1基因杂合突变,其编码核苷酸序列第389位的胸腺嘧啶突变为鸟嘌呤（c.389T〉G）,相应氨基酸序列的第130位亮氨酸变为精氨酸（p.L130R）。该突变改变了进化上保守的氨基酸序列并被预测为有致病性,功能研究揭示突变型HAND1的转录激活功能显著降低。结论：该HAND1基因功能缺失性新突变可能是CHD的少见分子病因。

英文摘要：

Objective： To study a novel mutation in the HAND1 gene associated with congenital heart disease （CHD）. Methods： A cohort of 136 children with CHD and a total of 200 healthy children as controls were recruited and their genomic DNAs were extracted. By direct polymerase chain reaction- sequencing, the HAND1 gene was screened for a novel mutation. The computer software was used to evaluate the conversation of the altered amino acid and to predict the pathogenic potential of the identified mutation. The dual-luciferase reporter assays were performed to explore the effect of the mutation on HAND1 function. Results：A novel heterozygous mutation, a substitution of guanine for thymine at the nucleotide position 389 （c. 389T〉G）, predicting the conversion of leueine into arginine at amino acid 130 （p. L130R）, was detected in a child with Fallot＇s tetralogy. The mutation altered the amino acid conserved evolutionarily, and was predicted to be causative. Functional studies revealed that the mutant HAND1 was associated with significantly decreased transcriptional activity. Conclusion.. The novel loss-of-function mutation of HAND1 identified in the present study is likely to be an uncommon molecular etiology responsible for CHD.