中国人群少见血红蛋白H病的分子遗传学特征分析

目的 分析由少见基因类型导致的血红蛋白H病家系的分子遗传学特征.方法 采用标准的血液学分析技术检测先证者及家系成员红细胞参数,包括RBC、Hb、MCV、MCH、MCHC和RDW,进行表型诊断.利用SPIFE快速自动电泳分析系统检测其血红蛋白组分Hb A、HbA2、Hb F、Hb H和Hb Bart＆#39;s.采用反向斑点杂交技术诊断α-地中海贫血基因非缺失突变,利用gap-PCR扩增特异位点序列并对扩增序列进行克隆测序,明确突变位点.结果 先证者母亲MCV、MCH均降低,Hb A2为2.39％且亨氏小体阳性,基因检测结果为α泰国型缺失杂合子.先证者父亲各红细胞参数正常,但RDB检测结果为携带αCS点突变.先证者及其弟表现为中重度小细胞低色素贫血,蛋白电泳结果显示他们均有Hb H和Hb Bart＆#39;s带,先证者Hb H为1o.8％,Hb Bart＆#39;s为7.51％,其弟Hb H为14.78％,Hb Bar（s为9.11％,基因检测结果证实该姐弟均为HbH病患者,遗传了母亲的α泰国型缺失片段和父亲的αCS点突变,故α地中海贫血型别为THAI/ααcs.结论 首次报道中国人群少见的H病类型THAI/α αcs地贫基因类型是中国人群少见的H病类型,丰富了中国人群α珠蛋白基因突变谱.

Analysis of the Molecular Characteristics of a Chinese Family with Hemoglobin H Disease

Objective To investigate the molecular characteristics of a Chinese family with hemoglobin H disease due to the rare a-thalassemia genotype. Methods Phenotypic analysis was performed using standard hematological tests tomeasure red blood cell parameters ,including RBC,Hb,MCV,MCH,MCHC, and RDW. SPIFE automatic Hb agarose gel electrophoresis was used to measure hemoglobin fraction Hb A, Hb A2, Hb F, Hb H, and Hb Bartrs. The alleles of α-tha- lassemia non-deletional mutation were determined by RDB assay. The α-thalassemia Thailand deletion （-THAI ） was de- tectable using allele specific gap PCR. The Thailand deletion was also verified by DNA sequencing. Results Alleles-spe- cific PCR analysis demonstrated that the probandls mother was heterozygoted for Thailand mutation, with lower MCV, MCH （70.2 fl,22.5 pg）. The probandrs father had normal red blood cell parameters, but acs mutation gene was positive with RDB. Both the proband and her brother suffered from severe anemia with hemoglobin 54 g/L and 77 g/L, respective- ly. Their MCV and MCH decreased with 66.6 fl,19.8 pg and 71.3 fl,19.1 pg,and the result of hemoglobin electrophoresis showed that both presented Hb H（10.8% and 14.78% respectively） and Hb Bart% （7.51% and 9.11% respectively）. All tests showed the proband and her brother inherited the Thailand deletion gene from their mother and aCSmutation gene from their father, so their α-thalassemia genotypes were THAI/ααcs. Conclusion THAI/ααCSis a rare genotype of α-thalassemia in Chinese Han population and is the first report in Guangdong province.