Craig J E, Sheerin S M, Barnetson R, Thein S L
MRC Molecular Haematology Unit, John Radcliffe Hospital, Oxford.
Br J Haematol. 1993 May;84(1):106-10. doi: 10.1111/j.1365-2141.1993.tb03032.x.
Single-base substitutions in the immediate 5'-flanking region of the fetal G gamma and A gamma globin genes have been associated with non-deletional forms of hereditary persistence of fetal haemoglobin (HPFH). Previously, the sole promoter mutation associated with HPFH in British individuals has been the T to C substitution at position -198 relative to the A gamma globin gene CAP site. We have investigated a British family with G gamma HPFH and found a T to C substitution at position -175 of the G gamma globin gene. The mutation was first detected by examining the amplified 5' regions of both the G gamma and A gamma globin genes for heteroduplex formation after electrophoresis in a Hydrolink gel. The potential of such a system for the study of sequence variations in the gamma gene promoter regions associated with elevated HbF expression has been evaluated. Previously reported cases of an identical mutation in an American-Black and a Sardinian family display haematological phenotypes remarkably similar to that of the British family described here.
胎儿Gγ和Aγ珠蛋白基因紧邻的5'侧翼区域中的单碱基替换与胎儿血红蛋白（HPFH）遗传性持续存在的非缺失形式有关。此前，在英国个体中与HPFH相关的唯一启动子突变是相对于Aγ珠蛋白基因CAP位点的-198位由T替换为C。我们研究了一个患有Gγ HPFH的英国家庭，发现Gγ珠蛋白基因的-175位存在由T替换为C的情况。该突变首先通过在Hydrolink凝胶中电泳后检查Gγ和Aγ珠蛋白基因扩增的5'区域中异源双链体的形成来检测。已评估了该系统用于研究与HbF表达升高相关的γ基因启动子区域序列变异的潜力。先前报道的一个美国黑人家庭和一个撒丁岛家庭中相同突变的病例表现出与这里描述的英国家庭非常相似的血液学表型。
