一个遗传性出血性毛细血管扩张症家系患者的ACVRL1基因突变分析

摘要

Objective To identify the activin A receptor typeⅡ-like I gene(ACfVRLI) mutations in a Chinesc family with hereditary hemorrhagic telangiectasia(HHT2).Methods The exons 3,7 and 8 of ACVRL1 gene of the proband and her five family members were amplified by polymerase chain reaction(PCR), and the PCR products were sequenced.Results The proband had obvious telangiectasis of gastric mucosa,and small arteriovenous fistula in the right kidney.All the patients in the HHT2 family had iterative epistaxis or bleeding in other sites.and had telangiectasis of nasal mucosa,tunica mucosa oris and finger tips.ACVILL1 gene analysis confirmed that there iS frameshift mutation caused by deletion of G145 in exon 3 in the 4 patients.but the mutation iS absent in 2 members without HHT2.Conclusion The HHT2 family is caused by a 145delG mutation ofACVRL1 gene,resulting in frameshift and a new stop codon at codon 53.%目的 确定一个遗传性出血性毛细血管扩张症家系患者ACVRL1基因突变位置及分析临床表型.方法 对该家系先证者ACVRL1基因常见突变位置第3、7、8外显子进行PCR和变性高效液相色谱方法筛查,随后DNA测序证实,确定突变位点后,扩增其家系另5名成员的相应区域筛查,并行DNA序列分析.结果 先证者胃黏膜见出血和毛细血管扩张,彩超显示右肾小动静脉瘘;4例患者ACVRL1基因第3外显子145delG,形成移码突变,导致第53密码子为UAG终止密码子,另2名无临床表现者未见此突变.结论 ACVRL1基因145delG突变是这个家系致病遗传基础.