Ⅱ型遗传性毛细血管扩张症临床特点和ACVRL1基因筛查

Clinical features and screening of ACVRL1 gene in II hereditary hemorrhagic telangiectasia

目的分析遗传性毛细血管扩张症（HHT）患者的临床特点和筛查致病基因。方法采集3个HHT家系患者临床资料，按照HHT的临床诊断标准进行确诊，对临床确诊的患者进行ACVRL1基因筛查及目标氨基酸序列保守性分析。结果3例先证者及另外1例被确诊为HHT，2例可疑为HHT。家系一中先证者及其长子ACVRL1基因cDNA第287位发生错义突变（c．287A〉G），导致ALK1蛋白第96位天冬酰胺变为丝氨酸（P.Asn96Ger）；家系二中2例患者ACVRL1基因cDNA第1271位发生错义突变（C．1271C〉T），导致ALK1蛋白第424位脯氨酸变为亮氨酸（P．Pr0424Leu）；家系三中先证者ACVRL1基因cDNA第147位发生缺失突变（O．147delC），候选密码子发生移码突变，ALK1蛋白在第53位氨基酸提前终止。通过多物种蛋白保守性分析证实上述突变位点在多物种之间保守，查询NCBI数据库证实上述突变不是单核苷酸多态性。结论对于临床确诊的HHT患者进行基因筛查，明确其致病基因，同时对其子女进行基因筛查，可在发病之前进行早期诊断和预防。

Objective To analyze the clinical features and pathogenic gene of the patients with hereditary hemorrhagic telangiectasia （HHT）. Methods The clinical features of 3 HHT families were collected. And the patients were diagnosed according to clinical diagnostic analyzed criteria of HHT, the ACVRL1 gene screened and the conservation of mutation protein. Results Three probands and 1 patient were diagnostic for HHT and 2 patients were suspected. In family I , there was a missense mutation of ACVRL1 gene in c. 287A 〉 G on 2 patients, leading to the transferal of amino acids from Asn to Ser at 96th place. In family I1 , there was a missense mutation of c. 1271C 〉 T on ACVRL1 in 2 patients, leading to the transfer of amino acids from Pro to Leu at 424＇h place. In family 11I, there was a deletion mutation of c. 147delC on ACVRL1 so as to produce only the former 53 amino acids of ALK1 protein. Through an analysis of multi-species conservation, the mutations were conserved between multiple species. By querying the National Center for Biotechnology Information （NCBI） database, we confirmed that the mutation was not of a single nucleotide polymorphism （SNP）. Conclusion The genetic screening of HHT patients may identify their virulence gene. And genetic screening of their offspring is helpful for the early diagnosis and prevention before disease onset.