地中海贫血的产前筛查和基因诊断

Prenatal screening and genetic diagnosis of thalassemia

目的分析孕妇血液学指标与地中海贫血（简称地贫）各基因型的关系，探讨地贫产前筛查的可靠依据。方法在本院所有产前检查人群中广泛开展地贫的血液学筛查，进行阳性病例基因检测，确诊后筛查配偶，夫妇患同型地贫者进行产前诊断；疑似β地贫夫妇行β基因突变热点测序、比对，探查未知突变。结果疑似地贫孕妇115例，确诊73例，夫妇同患α地贫1对、β地贫3对，产前诊断重型地贫患儿3例。Hb、MCV、RBC、RDW、HbA2在α、β、α／β与β/β间差异有统计学意义（P〈0．01）。疑似β地贫的样本大多呈2-5个SNP杂合状态。结论重庆为β地贫的高发区，红细胞参数和定量血红蛋白电泳是筛查地贫的重要指标，gap-PCR、PCR-RDB、基因测序可明确诊断，切实干预地贫的出生缺陷。

Objective To explore reliable evidences for thalassemic prenatal screening by investigating the corresponding relationship of hematologic indexes and thalassemic genotypes in pregnant women. Mαhods Generally hematologic dαection for thalassemia was carried out on the peripheral venous blood samples of all prenatal checked-up expectant mother. Those suspectable thalassemic sufferers were further identified by gene diagnosis, and then the husband was dαected when his wife was thalassemic patient. For the couple with same thalassemia genαype, prenatal diagnosis was conducted. Genes of suspectable β-thalassemic couples were sequenced, and mutational hot spots of β-globin were studied by BLAST to explore unknown mutation. Results Totally 115 pregnant women were suspectable thalassemia, and 73 cases among them were final diagnosed. There was 1 couple of simultaneous α-thalassemia, and 3 couples of β-thalassemia. Prenatal diagnosis found 3 fαuses with serious thalassemia. Hb, MCV, RBC, RDW and HbA2 had statistical significance bαween α, β, （α/β and β/β （P 〈 0.01 ）. There were about 2 to 5 SNP in the suspectable β-thalassemia. Conclusion Thalassemia is quite common in Chongqing. Red cell paramαers and quantitative hemoglobin electrophoresis are important in all screening indexes. Gap-PCR, PCR-RDB and genαic sequences analysis should be used to diagnose exactly so as to prevent thalassemic birth defect.