Manca L, Cocco E, Gallisai D, Masala B, Gilman J G
Institute of General Physiology and Biological Chemistry, University of Sassari, Italy.
Br J Haematol. 1991 May;78(1):105-7. doi: 10.1111/j.1365-2141.1991.tb04390.x.
In Sardinia, the beta-39 nonsense mutation is the primary cause of beta 0-thalassaemia. This mutation is found mainly on beta-globin gene cluster haplotypes I and II, which differ in their A gamma globin types (A gamma I and A gamma T, respectively). This report presents data on G gamma, A gamma I and A gamma T levels, and the presence or absence of a 4 base pair (bp) deletion at -225 to -222 of the A gamma globin promoter, in 55 poly-transfused beta 0-thalassaemia major patients. Six patients were homozygotes for the normal (N) A gamma promoter lacking the 4 bp deletion, had no A gamma T globin, and their mean G gamma:A gamma I: A gamma T ratio was 52.9:47.1:0. Twenty-five patients were homozygotes for the mutant (M) A gamma promoter with the 4 bp deletion, had no A gamma I globin, and the mean G gamma:A gamma I: A gamma T ratio was 62.1:0:37.9. For M/M compared to N/N, the lower A gamma T than A gamma I was significant by the t-test (P less than 0.001). Twenty-four N/M cases had mean G gamma:A gamma I:A gamma T of 56:24.4:19.6, and the lower A gamma T than A gamma I was also significant (P less than 0.001). Partial haplotype analysis on these and 17 other beta 0-thalassaemia patients suggested that the 4 bp deletion was strongly associated with haplotype II. Of 33 M/M, 32 were haplotype II/II and one was II/5a; of 31 N/M, 29 were I/II and two were II/IX; of eight N/N, seven were haplotype I/I and one was I/IX. These data show a strong association of the 4 bp promoter deletion with decreased expression of the A gamma T globin gene on haplotype II.
在撒丁岛，β-39无义突变是β0地中海贫血的主要病因。该突变主要见于β珠蛋白基因簇单倍型I和II，它们的Aγ珠蛋白类型不同（分别为AγI和AγT）。本报告展示了55例多次输血的重型β0地中海贫血患者的Gγ、AγI和AγT水平数据，以及Aγ珠蛋白启动子-225至-222处4个碱基对（bp）缺失的有无情况。6例患者为正常（N）Aγ启动子的纯合子，无4 bp缺失，无AγT珠蛋白，其平均Gγ:AγI:AγT比值为52.9:47.1:0。25例患者为具有4 bp缺失的突变（M）Aγ启动子的纯合子，无AγI珠蛋白，平均Gγ:AγI:AγT比值为62.1:0:37.9。对于M/M与N/N相比，经t检验，AγT低于AγI具有显著性（P<0.001）。24例N/M病例的平均Gγ:AγI:AγT为56:24.4:19.6，AγT低于AγI也具有显著性（P<0.001）。对这些患者以及另外17例β0地中海贫血患者进行的部分单倍型分析表明，4 bp缺失与单倍型II密切相关。在33例M/M中，32例为单倍型II/II，1例为II/5a；在31例N/M中，29例为I/II，2例为II/IX；在8例N/N中，7例为单倍型I/I，1例为I/IX。这些数据表明，4 bp启动子缺失与单倍型II上AγT珠蛋白基因表达降低密切相关。
