Garewal Gurjeewan, Das Reena, Ahluwalia Jasmina, Marwaha R K, Varma S
Department of Haematology, Postgraduate Institute of Medical Education & Research, Chandigarh, India.
Am J Hematol. 2005 Aug;79(4):252-6. doi: 10.1002/ajh.20445.
A study of beta-gene mutations in Jat Sikhs, a subcaste of Punjabis, revealed a very high prevalence (46%: 41/88) of the mild beta++ promoter region mutation -88 (C-T). Sixteen individuals presenting in homozygous form were clinically mild. Un-transfused patients had characteristic hematological findings: high Hb F (38.1-68.6%, mean 47.4%), high Hb A2 (5.7-9.8%, mean 6.88%), and the rest had adult hemoglobin. The 19 subjects with compound heterozygosity for -88 (C-T) and another beta-gene mutation presented both as thalassemia intermedia (four cases) and as thalassemia major (15 cases). One of the four patients with the milder phenotype had a second mild mutation, CAP+1 (beta++). In the other three cases with the milder phenotype, the second mutation was associated with the presence of the XmnI Ggamma polymorphism. Notably, the XmnI Ggamma was negative in all the -88 (C-T) alleles. None of the patients had associated alpha-thalassemia even in the thalassemia intermedia group. Haplotype analysis of the -88 (C-T) homozygous cases showed a single haplotype (+ - - - - + -) in all but two individuals. This haplotype is distinct from those described in the Africans with homozygous -88 (C-T), suggesting that the mutation in our population occurred independently.
一项针对旁遮普人一个亚种贾特锡克人的β基因突变研究显示，轻度β++启动子区域-88（C-T）突变的患病率非常高（46%：41/88）。16名呈纯合形式的个体临床症状较轻。未输血的患者有典型的血液学表现：高Hb F（38.1 - 68.6%，平均47.4%）、高Hb A2（5.7 - 9.8%，平均6.88%），其余患者为成人血红蛋白。19名-88（C-T）与另一种β基因突变的复合杂合子受试者表现为中间型地中海贫血（4例）和重型地中海贫血（15例）。4例表型较轻的患者中有1例有第二个轻度突变，即CAP +1（β++）。在其他3例表型较轻的病例中，第二个突变与XmnI Gγ多态性的存在有关。值得注意的是，所有-88（C-T）等位基因中的XmnI Gγ均为阴性。即使在中间型地中海贫血组中，也没有患者伴有α地中海贫血。-88（C-T）纯合病例的单倍型分析显示，除2名个体外，所有个体均为单一单倍型（+ - - - - + -）。该单倍型与非洲纯合-88（C-T）个体中描述的单倍型不同，表明我们人群中的突变是独立发生的。
