3例罕见地中海贫血家系分子诊断和产前诊断

目的:对产前地中海贫血筛查阳性的患者及其胎儿进行地中海贫血基因分析,并对先证者进行家系调查。方法:通过血常规及血红蛋白组分进行表型分析,采用断裂聚合酶链反应检测4种α-地中海贫血基因缺失;采用聚合酶链反应/反向斑点杂交法检测17种常见β-地中海贫血基因点突变,对于未发现常见突变者采用β-珠蛋白基因DNA测序。结果:3个家庭先证者均有MCV和MCH降低的血液学表型,临床常规试剂未检出3种α-地中海贫血基因缺失和17种β-地中海贫血基因点突变。经基因测序,先证者1及其父亲为罕见β-地中海贫血-86(C>G)突变杂合子,胎儿未检见;先症者2及其母亲为泰国型缺失杂合子(--THAI/αα),胎儿为泰国型合并东南亚型缺失(--TAIL/--SEA)的巴氏水肿胎;先症者3为泰国型缺失杂合子(--THAI/αα),胎儿为泰国型合并东南亚型缺失(--TAIL/--SEA)的巴氏水肿胎。结论:有明显血液学表型在排除常见地中海贫血基因突变类型的患者,应该采用其它方法进一步确诊以防漏检。

Molecular and prenatal diagnosis and pedigree investigation for 3 cases of rare thalassemia

Objective: To analyze thalassemia gene in positive patients and fetuses,and to investigate pedigree status.Methods: Phenotypic analysis was performed by routine examination and hemoglobin components analysis,and 4 kinds of α-thalassemia gene deletion was detected by PCR;17 kinds of common β-thalassemia point mutation were detect by PCR-RDB,and negative samples were analyzed by β-globin gene DNA sequencing.Results: Probands of 3 families showed reduced MCV and MCH,but no detection of α-thalassemia gene deletion or 17 kinds of commonβ-thalassemia point mutation by routine examination.Gene sequencing showed that proband 1 and his father had rare heterozygousβ-thalassemia-86(C>G),and the fetus was negative;proband 2 and his mother had deletion heterozygote in Thailand type(——THAI/αα),and the fetus had Hb Bart’s hydrops fetalis with merger of Thailand and Southeast Asia type deletion(——TAIL/——SEA);proband 3 had deletion heterozygote in Thailand type(——THAI/αα),and the fetus had Hb Bart’s hydrops fetalis with merger of Thailand and Southeast Asia type deletion(——TAIL/——SEA).Conclusions: Further detection should be performed to exclud common thalassemia gene mutation in patients with significant hematologic phenotype.