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目的 探查一个Ⅳ型埃勒斯-当洛斯综合征(EDS Ⅳ)家庭Ⅲ型胶原蛋白基因α1(COL3A1)的致病突变.方法 采集患者及其妻儿的外周血,并提取脱氧核糖核酸(DNA),通过Sanger测序法获取患者COL3A1基因变异,将结果与200名正常人的测序结果进行对比,并在单核苷酸多态性数据库(dbSNP)、千人基因组计划(TGP)数据库、炎黄(YH)数据库、外显子测序计划(ESP)数据库中进行检索,排除其为单核苷酸多肽性(SNPs).利用突变筛查软件(SIFT)、突变评价软件(MutationTaster)以及2代多态性表型预测软件(PolyPhen-2)对变异进行预测,最后将变异在人类基因突变数据库(HGMD)、Pubmed、万方、中国知网(CN-KI)以及谷歌学术中搜索,查看其是否已被报道.结果 发现COL3A1基因变异c.3256G>C(p.G1086R)在正常人的测序结果中不存在,并且在上述各数据库中均无相关记录,谷歌学术中亦无文献报道.三大预测软件预测结果均为有害.结论 COL3A1基因上的变异c.3256G>C为一个新发现的致病突变.“,”Objective To identify the causal mutation in a family with Ehlers-Danlos syndrome Ⅳ (EDS Ⅳ). Methods The peripheral blood of the patients and their family was collected to extract deoxyribonucleic acid (DNA). The variant was identified by Sanger sequencing of collagentype Ⅲ alpha 1 (COL3A1) gene and detected in 200 normal persons. Then it was searched in database of single nucleotide polymorphisms (dbSNP), 1 000 Genomes Project (TGP) database, YanHuang (YH) database and exome sequencing project (ESP) database while the SNP was excluded. The vari6ant was predicted by three online softwares: SIFT, Mutation Tasterand PolyPhen-2. At last, it was searched in Human Gene Mutation Database (HGMD), Pubmed, Wan Fang, CNKI and Google scholar to confirm that weather it had been reported before. Results We found that c.3256G>C(p.G1086R)was not detected in normal persons. It was not found in all the databases mentioned above as well as Google scholar. All the three online softwares predicted this variant to be deleterious to the protein function. Conclusion The 3256G>C(p.G1086R) gene variation from COL3A1 is a new disease-causing mutation.