中间型β地中海贫血的基因诊断  

Molecular diagnosis of β thalassemia intermedia

作　　者：陈坚[1,2] 刘炜培[1,2] 陈美珏[1,2] 盛敏[1,2] 任兆瑞[1,2] 周润甜 黄淑帧[1,2] 曾溢滔[1,2] 

机构地区：[1]上海市儿童医院上海医学遗传研究所 [2]广东省佛山市第一人民医院

出　　处：《中华医学杂志》1997年第8期575-578,共4页National Medical Journal of China

基　　金：国家自然科学基金;卫生部科学基金

摘　　要：研究中间型β地中海贫血（地贫）的分子缺陷，为中间型β地中海贫血的基因诊断和产前诊断提供科学依据。方法应用Ｓｏｕｔｈｅｒｎ印迹杂交、多重等位基因特异聚合酶链反应（ＭＡＳ－ＰＣＲ）、双链ＤＮＡ循环测序和珠蛋白肽链生物合成速率测定等技术，对１４例中间型β地贫病例进行了血液学、珠蛋白基因（α、β和γ）以及珠蛋白肽链生物合成速率的分析。并对２５０例脐带血的α珠蛋白基因组织进行了鉴定。结果１４例β地贫病人中４例为β地贫杂合子复合右侧和（或）左侧不等交换型α珠蛋白基因增多（ααａｎｔｉ３．７和／或αααａｎｔｉ４．２），３例为β地贫遗传复合体复合α珠蛋白基因减少，１例为β地贫遗传复合体复合γ珠蛋白基因上游启动区－１５８ｎｔＣ→Ｔ的突变杂合子，６例的α和Ｇγ珠蛋白基因未见异常。对２５０例脐带血共５００条染色体的α珠蛋白基因的分析表明，共有８条染色体的α珠蛋白基因异常，占染色体总数的１．６％，其中—ＳＥＡ１条，α－３．７４条，αααａｎｔｉ３．７３条。结论除β地贫基因纯合子或遗传复合体复合α珠蛋白基因缺失外，β地贫基因杂合子复合α珠蛋白基因增多是导致中间型β地中海贫血的又一种重要的分子病因。Objectives To analyze the molecular abnormalities of β thalassemia intermedia and contribute to the knowledge of the molecular diagnosis and prenatal diagnosis of this disorder. Methods In 14 patients with β thalassemia intermedia, we analyzed the hematologies, α, β and γ globin gene organization and structure as well as globin gene biosynthesis by Southern blot hybridization, multiplex allale specific PCR (MAS PCR), DNA sequencing and micro globin chain biosynthetic assay. Moreover, α globin gene organization was studied in 250 cord blood specimens. Results Of the 14 patients, 4 were found to be β thalassemia heterozygotes combined with rightward cross over or/and leftward cross over triplicated haplotype of α globin gene loci (ααα anti3 7 or/and ααα anti4 2 ), 3 were compound heterozygotes for β thalassemia combined with α thalassemia 1 or 2, one was identified to be a compound heterozygote for β thalassemia combined with Gγ promotor 158 (C→T) mutation. The data of the α globin gene organization in 250 cord blood specimens showed that 8 of the 500 tested chromosomes (1.6%) were abnormal: 3 were ααα anti3 7 , 4 were α -3.7 , and one was SEA . Conclusion In addition to β thalassemia homozygote or compound heterozygotes with α thalassemia, the conjunctive abnormalities of β thalassemia heterozygote with α globin gene triplication was another major cause of β thalassemia intermedia.

关 键 词：Β地中海贫血 珠蛋白基因 诊断 

分 类 号：R556.610.4[医药卫生—血液循环系统疾病] R446.9[医药卫生—内科学]