遗传性出血性毛细血管扩张症一家系ALK1基因突变研究

Mutation analysis of ALK-1 gene in a Chinese family with hereditary hemorrhagic telangiectasis type Ⅱ

目的:研究遗传性出血性毛细血管扩张症(HHT)一家系ALK1基因突变情况,分析基因型与表现型之间的关系。方法:收集1例HHT家系,采用聚合酶链反应(PCR)扩增该家系成员的ALK1基因全部编码外显子及其侧翼序列,并对PCR产物进行序列分析,以家系中的健康者和100例无血缘关系的正常人作对照。结果:该家系中所有患者均出现ALK1基因的错义突变c.1010T>C(p.L337P),即第1010位碱基由胸腺嘧啶(T)突变为胞嘧啶(C),使得ALK1基因第7号外显子第337位密码子由CTG变为CCG,导致正常的亮氨酸被脯氨酸替代。结论:ALK1基因的错义突变c.1010T>C(p.L337P)是导致该家系临床表型的主要原因。

Objective： To identify the mutation of ALK- 1 gene in a Chinese family with hereditary hemorrhagic telangiectasis （HHT） type II. Methhods： All the coding exons of ALK - 1 gene were amplified by polymerase chain reaction and the products were detected by direct s^uencing analysis. The mutation results of the patients were com- pared with the normal members of the same family and other 100 unrelated control individuals. Results： A missense mutation c. 1010T〉 C （p.L337P） of ALK- 1 gene was identified in all the patients of the family, but did not found in the controls. Conclusion： The c. 1010T 〉 C （p. L337P） mutation of ALK - 1 gene seems to be the pathologic cause of the Chinese family with HHT type II.