Ottolenghi S, Giglioni B, Pulazzini A, Comi P, Camaschella C, Serra A, Guerrasio A, Saglio G
Blood. 1987 Apr;69(4):1058-61.
Selective overexpression (50- to 100-fold) in adult erythroid cells of either G gamma or A gamma fetal globin gene is observed in hereditary conditions known as delta beta zero-thalassemia and hereditary persistence of fetal hemoglobin (HPFH). Recently, a C----T change at position -196 of an overexpressed A gamma globin gene from an Italian HPFH was hypothesized, on the basis of indirect evidence, to represent the cause of the functional defect. We now show that the same mutation is present in a different overexpressed A gamma-globin gene from a Sardinian patient with a different syndrome (delta beta zero-thalassemia). The Sardinian A gamma globin gene differs from both the HPFH and the normal A gamma globin gene at nucleotide 1,560 in the noncoding portion of the third exon, where an A is deleted. In addition, the mutant -196 A gamma-globin gene is linked to a normal beta globin gene in HPFH, and to a beta-thalassemic gene (beta 39CAG----TAG) in delta beta zero-thalassemia. These data strengthen the suggestion that -196 mutation is causally linked to the abnormal phenotype and raise the question of whether the same or multiple mutational events are responsible for the appearance of the -196 mutation in different syndromes.
在称为δβ0地中海贫血和胎儿血红蛋白遗传性持续存在（HPFH）的遗传性疾病中，观察到成人红系细胞中Gγ或Aγ胎儿珠蛋白基因的选择性过表达（50至100倍）。最近，基于间接证据推测，来自一名意大利HPFH患者的过表达Aγ珠蛋白基因-196位的C→T变化代表功能缺陷的原因。我们现在表明，一名患有不同综合征（δβ0地中海贫血）的撒丁岛患者的另一个过表达Aγ珠蛋白基因中存在相同的突变。撒丁岛Aγ珠蛋白基因在第三外显子非编码部分的核苷酸1560处与HPFH和正常Aγ珠蛋白基因不同，此处缺失一个A。此外，突变的-196 Aγ珠蛋白基因在HPFH中与正常β珠蛋白基因连锁，在δβ0地中海贫血中与β地中海贫血基因（β39CAG→TAG）连锁。这些数据强化了-196突变与异常表型存在因果关系的观点，并提出了在不同综合征中-196突变的出现是由相同还是多个突变事件导致的问题。
