遗传性出血性毛细血管扩张症一家系致病基因分析及沙利度胺治疗疗效观察

发布时间：2018-04-04 12:00

  本文选题：遗传性出血性毛细血管扩张症　切入点：基因突变　出处：《中国实验血液学杂志》2017年04期

【摘要】：目的:分析遗传性出血性毛细血管扩张症(hereditary hemorrhagic telangiectasia,HHT)一家系ACVRL1、ENG和MADH4(SMAD4)基因突变,并观察沙利度胺对其治疗的疗效。方法:对该家系进行详细的家系调查,采用PCR方法对先证者进行ACVRL1、ENG和SMAD4基因全部外显子序列扩增,应用Sanger测序法进行序列分析,将结果与数据库参照序列进行对比;对检测到的可疑突变在纳入研究的其他7名家系成员中进一步进行检测。先证者采用沙利度胺(100 mg/d)治疗6个月,而后观察其出血频率、出血量、输血频率等,评估疗效。结果:先证者(Ⅱ-1)及其另外4名家系成员(Ⅱ-2、Ⅲ-1、Ⅲ-2、Ⅲ-3)均存在有ACVRL1基因c.1231CT杂合突变,与临床表型共分离,为文献已经报道的突变;同时该家系部分成员(Ⅱ-1、Ⅱ-3,Ⅲ-1、Ⅲ-2)存在有ENG基因c.1096GC突变,不与临床表型共分离,为数据库收录的基因多态性;SMAD4基因未见突变。经沙利度胺治疗后,先证者出血频率、出血量、输血频率均减少,血红蛋白浓度和血清铁均升高。结论:HHT具有表型异质性,且随着年龄增长表型增多;ACVRL1基因c.1231CT突变是该家系的致病基因。沙利度胺对遗传性出血性毛细血管扩张症出血具有较好的疗效。
[Abstract]:Objective: to analyze the mutation of ACVRL1ENG and MADH4 SMAD4 gene in a family of hereditary hemorrhagic telangiectasia HHT, and to observe the therapeutic effect of thalidomide on it.Methods: the families were investigated in detail. All exon sequences of ACVRL1ENG and SMAD4 gene were amplified by PCR method. The sequence analysis was carried out by Sanger sequencing method, and the results were compared with the reference sequences of the database.Suspicious mutations detected were further detected in seven other family members included in the study.The proband was treated with thalidomide 100 mg / d for 6 months.Results: ACVRL1 gene c.1231CT heterozygosity was found in proband (鈪，

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