本文選題：遺傳性出血性毛細血管擴張癥　切入點：基因突變　出處：《中國實驗血液學(xué)雜志》2017年04期

【摘要】：目的:分析遺傳性出血性毛細血管擴張癥(hereditary hemorrhagic telangiectasia,HHT)一家系A(chǔ)CVRL1、ENG和MADH4(SMAD4)基因突變,并觀察沙利度胺對其治療的療效。方法:對該家系進行詳細的家系調(diào)查,采用PCR方法對先證者進行ACVRL1、ENG和SMAD4基因全部外顯子序列擴增,應(yīng)用Sanger測序法進行序列分析,將結(jié)果與數(shù)據(jù)庫參照序列進行對比;對檢測到的可疑突變在納入研究的其他7名家系成員中進一步進行檢測。先證者采用沙利度胺(100 mg/d)治療6個月,而后觀察其出血頻率、出血量、輸血頻率等,評估療效。結(jié)果:先證者(Ⅱ-1)及其另外4名家系成員(Ⅱ-2、Ⅲ-1、Ⅲ-2、Ⅲ-3)均存在有ACVRL1基因c.1231CT雜合突變,與臨床表型共分離,為文獻已經(jīng)報道的突變;同時該家系部分成員(Ⅱ-1、Ⅱ-3,Ⅲ-1、Ⅲ-2)存在有ENG基因c.1096GC突變,不與臨床表型共分離,為數(shù)據(jù)庫收錄的基因多態(tài)性;SMAD4基因未見突變。經(jīng)沙利度胺治療后,先證者出血頻率、出血量、輸血頻率均減少,血紅蛋白濃度和血清鐵均升高。結(jié)論:HHT具有表型異質(zhì)性,且隨著年齡增長表型增多;ACVRL1基因c.1231CT突變是該家系的致病基因。沙利度胺對遺傳性出血性毛細血管擴張癥出血具有較好的療效。
[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，

本文編號：1709866