Giampaolo A, Mavilio F, Massa A, Gabbianelli M, Guerriero R, Sposi N M, Caré A, Cianciulli P, Tentori L, Marinucci M
Br J Haematol. 1984 Jan;56(1):79-85. doi: 10.1111/j.1365-2141.1984.tb01273.x.
Fifty-one subjects originating from Southern Italy and affected by Cooley's anaemia have been studied in order to define the degree of heterogeneity of beta thalassaemia mutations in this high incidence area. Restriction endonuclease mapping has been carried out on genomic DNA by the Southern blot technique both to exclude the existence of gross deletions or rearrangements and to establish the relative frequency of four polymorphic restriction sites (i.e. G gamma and A gamma Hind III, beta Ava II and beta Bam HI) within the gamma delta beta gene region. In 28 subjects unequivocal linkage of the four polymorphic sites has been determined leading to the identification of seven different chromosome haplotypes, six of which had previously been reported associated with specific beta(0) and beta(+) thalassaemia mutations. Globin chain synthesis studies on peripheral blood reticulocytes indicated that subjects carrying the same genotype may behave differently as far as the beta chain production is concerned relative to both the alpha and the non-alpha chains. Thus, beta thalassaemia turns out to be quite heterogeneous even in this limited geographical area. Beta(+) mutations appear to be predominant, particularly those affecting nuclear precursor RNA splicing to mature beta globin mRNA.
为了确定在这个地中海贫血高发病率地区β地中海贫血突变的异质性程度，对来自意大利南部且患有库利氏贫血的51名受试者进行了研究。采用Southern印迹技术对基因组DNA进行限制性内切酶图谱分析，以排除大片段缺失或重排的存在，并确定γδβ基因区域内四个多态性限制性位点（即Gγ和Aγ Hind III、β Ava II和β Bam HI）的相对频率。在28名受试者中确定了这四个多态性位点的明确连锁关系，从而鉴定出七种不同的染色体单倍型，其中六种先前已报道与特定的β⁰和β⁺地中海贫血突变相关。对外周血网织红细胞的珠蛋白链合成研究表明，就β链产生而言，携带相同基因型的受试者相对于α链和非α链的表现可能不同。因此，即使在这个有限的地理区域，β地中海贫血也表现出相当大的异质性。β⁺突变似乎占主导地位，尤其是那些影响核前体RNA剪接成成熟β珠蛋白mRNA的突变。
