中国北方汉族人群神经管缺陷患儿DACT1基因突变分析

Mutation analysis on DACT1 gene in children with neural tube defects in northern Chinese Han population

目的探讨中国北方汉族人群神经管缺陷(NTDs)患儿与DACT1基因的相关性,为疾病的诊断及遗传咨询提供依据。方法收集163例NTDs患者和480例无亲缘关系健康个体的外周血标本,采用聚合酶链反应和DNA直接测序的方法检测DACT1基因的突变情况,并对突变位点进行生物信息学分析。结果在NTDs患者中发现6个突变位点,有4个突变位点为错义突变,分别为p.R45W、p.D142G、p.N356K、p.V702G,在正常对照中未检测到这些突变位点。其中3个位点的氨基酸残基(p.45R、p.142D、p.356N)在进化上高度保守,且这3个位点突变携带者均为女性,同时存在无脑畸形。结论中国北方汉族人群NTDs患者存在DACT1基因突变,且可能为该病风险因素之一。

Objective To investigate the correlation between neural tube defects (NTDs) and DACT1 gene, and provide the basic data for disease diagnosis and genetic counseling. Methods Blood samples were obtained from 163 NTDs patients and 480 unrelated healthy individuals. Mutation detection of DACT1 gene and DNA direct sequencing was carried out by PCR amplification. Bioinformatics analysis of these mutated loci was performed. Results Six mutations were found in NTDs patients, including 4 missense mutations (p.R45W, p.D142G, p.N356K and p.V702G). But these mutations were not found in 480 healthy individuals. Three mutated amino acid residues (p.45R, p.142D and p.356N) were highly conservative in evolution, and the mutated carriers were female patients, and suffered from anencephaly. Conclusion DACT1 gene mutation may be a risk factor of NTDs in Han population of northern China.