遗传性出血性毛细血管扩张症一家系ALK1基因突变研究和临床微创治疗

Mutation analysis of ALK-1 gene in a Chinese family with hereditary hemorrhagic telangiectasis type II and its minimally invasive treatment in clinic

目的研究遗传性出血性毛细血管扩张症(hereditary hemorrhagic telangiectasis,HHT)一家系活化素受体激酶1(activin receptor-like kinase-1,ACVRL1或ALK1)基因突变情况,评估双极电凝治疗鼻出血的疗效。方法收集1例HHT家系,采用聚合酶链反应(polymerase chain reaction,PCR)扩增其成员ALK1基因全部编码外显子及侧翼序列,对PCR产物进行序列分析,以其健康者和100例无血缘关系的正常人作对照。12名患者鼻出血时应用鼻内镜下双极电凝止血术43例(次)。结果所有患者均出现ALK1基因的错义突变c.1010T>C(p.L337P),对照组未发现此突变。采用鼻内镜下双极电凝止血术,有效止血,且复发时间较治疗前明显延长,复发频率延长至1个月～1年以上,2例两年无出血症状。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,鼻内镜下双极电凝止血术处理此类病变效果良好。

OBJECTIVE To identify the mutation of ALK-1 gene in a Chinese family with hereditary hemorrhagic telangiectasis （HHT） type Ⅱ. The common clinical symptoms of this disease is nasal bleeding which is ceased by bipolar coagulation. METHODS All the coding exons and flanking sequence of ALK-1 gene were amplified by Polymerase chain reaction and the products were detected by direct sequencing analysis. The mutation results of the patients were compared with the normal members of the same family and other 100 individuals without blood relation, we applied bipolar coagulation to cease the nasal bleeding under endoscope for the 12 patients of that pedigree （43 times） . RESULTS A missense mutation c.1010T〉C （p.L337P） of ALK-1 gene was identified in all the patients of the family except the controls. It was effective to deal with the nasal bleeding by bipolar coagulation under endoscope. The interval of relapse was markedly extended than before and often extended from 1 month to 1 year long. Two patients hadn＇t cause nose bleeding for two years.CONCLUSION The c.1010T〉C （p.L337P） mutation of ALK-1 gene seems to be the main cause which was involved in the phenotypic of this Chinese family with HHT type Ⅱ. It will have good results to deal with nosebleed with bipolar coagulation under endoscope.