中间型β地中海贫血家系基因分子生物学特征分析  

Molecular characterization of a family with beta-thalassemia interinedia

作　　者：荣卡彬[1] 黄革[1] 蒋文玲[1] 李运雄[1] 罗宪玲[1] 孟锦绣[1] 余细勇[1] 

机构地区：[1]广东省人民医院医学研究中心广东省医学科学院,广州510080

出　　处：《中华检验医学杂志》2009年第4期412-416,共5页Chinese Journal of Laboratory Medicine

摘　　要：目的分析在中国人群中发现的中间型β地中海贫血家系的分子生物学特征。方法表型检测采用标准的血液学分析技术测量RBC参数，采用高效液相色谱方法检测Hb组分。采用反向斑点杂交技术诊断β地中海贫血基因突变，利用跨越断裂点PCR技术（gap—PCR）扩增断裂点基因序列并进行测序分析。结果先证者Hb浓度为86g/L，属中间型地中海贫血表型。先证者父亲呈典型的小细胞低色素改变，平均红细胞容积（MCV）为63．7n，平均红细胞血红蛋白量（MCH）为20．4pg，均降低；血红蛋白A2（HbA2）增加，属地中海贫血杂合子表型。而先证者母亲、外祖母和妹妹的MCV及MCH均正常，但胎儿血红蛋白（HbF）较高，HbF分别为28．3％、21．1％及33．7％，属于胎儿血红蛋白持存综合征（HPFH）杂合子表型。进一步的基因分析表明，先证者为β^41-42／HPFH-6基因型的中间型地中海贫血患儿，其父母基因型分别为β^41-42／β^N和HPFH-6杂合子。其外祖母和妹妹均为HPFH-6杂合子。结论发现1例β^41-42／HPFH-6中间型地中海贫血病例，可为产前诊断提供可借鉴的临床经验。Objective To analyze a rare genotype with β-thalassemia intermedia. Methods Phenotypic analysis was performed using routine hematological tests to measure red blood cell parameters and high performance liquid chromatography （HPLC） was used to measure hemoglobin fractions. The β-globin gene mutations were conducted using reverse-dot-blot and DNA sequencing of the breakpoint region were characterized with gap-PCR. Results The proband had a trait of thalassemia intermedia with reduced hemoglobin （86 g/L）. The proband＇s father had a trait of microcytic hypochromic with reduced mean corpuscular volume（ MCV）, mean corpuscular hemoglobin （MCH） （ 63.7 fl and 20. 4 pg, respectively） and an elevated level of HbA2. He had the phenotype of heterozygosity for β-thalassemia. The proband＇s mother, grandmother and sister had a trait of heterozygote for hereditary persistence of fetal hemoglobin （HPFH） with elevated level of HbF, which were 28.3%, 21.1% and 33.7%, respectively. After molecular characterization of the family members, the proband was identified as a patient with β-thalassemia intermedia caused by co-existence of β-thalassemia（ β41-42 ） and HPFH-6. The father was heterozygous for β-thalassemia （β41-42/β^N） and the mother, grandmother and sister were all heterozygous for HPFH-6. Conclusions A rare β-thalassemia intermedia case resulting from compound heterozygote of β^41-42 with HPFH-6 is found. This study may provide clinical experiences for antenatal diagnosis.

关 键 词：Β地中海贫血 胎儿血红蛋白 系谱 聚合酶链反应 

分 类 号：R686[医药卫生—骨科学]