【摘要】 目的　探讨血红蛋白H(HbH)病患儿的基因型在预测该病临床表现中的价值以及影响该病进程的因素。方法　采用已建立的技术和方法检测 4 3例珠海市户籍HbH病患儿的基因型 ,测定其所有的血液学指标并详细记录其临床资料 ,分析其基因型与临床表现的关系。结果　 4 3例HbH病患儿中 ,检出 6种α 地中海贫血基因并相互组合产生 5种HbH病基因型 ,其中 α3 7/ SEA(2 6例 ,6 0 % )、 α4 2 / SEA(8例 ,19% )和αCSα/ SEA(5例 ,12 % )是该地区人群中 3种主要的HbH病分子缺陷类型。与 α3 7/ SEA相比 ,非缺失型 (αTα/ SEA)HbH病患儿的红细胞计数 (RBC)、血红蛋白 (Hb)、红细胞平均血红蛋白浓度 (MCHC)和血红蛋白A2 (HbA2 )值偏低 (P <0 0 5、0 0 1、0 0 1和 0 0 1) ,而红细胞平均体积 (MCV)和HbH水平则偏高 (P <0 0 1) ,且有较严重的临床表现。而与 α4 2 / SEA组相比 ,αTα/ SEA无论在血液学指标上 ,还是临床表现上的差异均不及与 α3 7/ SEA组比较为显著。并发现HbH水平与红细胞计数呈负相关 (r=- 0 39,P <0 0 0 1)。结论　HbH病患儿的临床表现主要与α 珠蛋白的基因型有关 ,αTα/ SEA型HbH病患儿有更严重的临床和血液学表现 , α4 2 / SEA次之 , α3 7/ SEA居末。但临床表现的严重性更多还原

【Abstract】 Objective Alpha-thalassemia is one of the most common monogene disorders in the world. Most frequently, it is caused by deletions of alpha-globin gene （-α or --）, and less commonly resulted from the non-deletional mutation（α^Tα）. Hemoglobin H （HbH） disease is the most severe type among survivors of alpha-thalassemia. The clinical presentation of children with the disease was highly heterogeneous. The aim of this study was to investigate the effect of alpha-globin genotypes in the children with HbH disease on predicting the phenotypic severity and to define the factors involved in the disease progress. Methods（Forty-three） children with the disease in Zhuhai area of Guangdong, China were examined by using established techniques to detect genotypes of α-globin and to determine all hematological parameters. All detailed clinical data of the cases were recorded. Then clinical and hematological findings, and the correlation with genotypes were evaluated. Results Six α-thalassemia mutations were detected and interacted to produce 5 HbH disease genotypes. Of these genotypes, -α^3.7/--^SEA（60%）, -α^4.2/--^SEA （19%） and α^CSα/--^SEA （12%） HbH diseases were prevalent in the area. Compared with -α^3.7/--^SEA HbH disease, significantly lower red blood cell （RBC） count, hemoglobin（Hb）, mean corpuscular hemoglobin （MCHC） and HbA₂（P<0.05, 0.01, 0.01 and 0.01, respectively）, and significantly higher mean corpuscular hemoglobin volume（MCV） and HbH levels （both P<0.01）, and more severe clinical phenotypes were found in the HbH disease with α^Tα/--^SEA genotype. While the differences were much more significant when compared with -α^3.7/--^SEA then compared with -α^4.2/--^SEA not only in the hematological parameters, but also in the severity of clinical phenotypes. In addition, HbH levels showed anegatively correlation with the RBC count （r=-0.39,P<0.01）. Conclusion The phenotypes of HbH disease may be mainly related to the underlying genotypes. The children with α^Tα/--^SEA genotype presented with more severe hematological and clinical phenotypes followed by the -α^4.2/--^SEA and then -α^3.7/--^SEA genotypes. But phenotypic severity was not simply related to the degree of α-globin deficiency. HbH levels were found to exacerbate anemia. These data might provide comprehensive and very valuable and basic information for the management of HbH disease , genetic counseling and prenatal diagnosis.更多还原