2例未知基因型地中海贫血的产前诊断

Prenatal diagnosis of 2 cases of unknown genotype thalassemia

目的探讨罕见未知基因型地中海贫血(以下简称地贫)的筛查、诊断与产前诊断,减少地贫的漏诊及误诊率,防止重型地贫患儿的出生。方法对中山市博爱医院产前诊断中心检查的2个家庭中通过血常规及血红蛋白电泳筛查可疑地贫的病例,采用gap-PCR、多重PCR及反向斑点杂交技术检测3种常见α-地贫基因缺失、4种少见缺失型α-地贫基因、3种常见的非缺失型α-地贫基因及17种常见β-地贫基因点突变,采用α-珠蛋白基因(α-基因)及β-珠蛋白基因(β-基因)DNA测序检测罕见致病突变。对血液学表型与基因型不符,疑存在未知地贫基因型的病例进行分析。结果 2个家庭先证者均有血液学表型与基因型不符情况,经分析:常规α-基因检测结果为--^(SEA)/--^(SEA)的先证者1为未知α-基因缺失合并东南亚型缺失的Hb H病;常规β-基因检测结果为β^(CD41-42)/β^(CD41-42)的先证者2为未知β-基因缺失合并β^(CD41-42)点突变所致的重型β-地贫,其母亲为未知β-基因缺失杂合子,胎儿为正常或者未知β-基因缺失杂合子。结论地贫基因检测结果应结合血液学表型分析,防止误诊。某些未知基因型的罕见地贫仍可行产前诊断,防止重型地贫儿的出生。

Objective To explore the methods for screening, diagnosis and prenateal diagnosis about unknown genotype thalassemia,and to reduce the misdiagnosis rate and to prevent the birth of children with severe thalassemia because of missed diagnosis. Methods Blood screening and automatic capillary electrophoresis were used in two families who examined in Bo＇ai Hospital of Zhongshan. For suspected members, we used gap - PCR to detect 3 most common deletional α- thalassemia, then used PCR -RDB to detect 3 most common non - deletional α- thalassemia and 17 kinds of β globin gene mutation. We used gene sequencing for the whole α - globin gene and β - globin gene to detect rare mutation. Cases suspected of the presence of unknown thalassemia genetypes were analyzed. Results Both families of probands have hematological phenotypes do not correspond to genes. Proband 1 with general gene result - - SEA/- SEA was suffering from HbH disease in fact, which was composed of unknown α- gene deletion and Southeast Asia deletion. Proband 2 with general gene result βCD41-42/βCD41-42 was suffering from transfusion - dependent β -thalassemia, which was composed of unknown β -gene deletion and βCD41-42 mutation. The mother was a heterozygote lacleing the unlenown gene, the fetus was normal or unknown 13 - gene deleted heterozygotes. Conclusion To prevent misdiagnosis and birth defects about babies with transfusion - dependent thalassemia, gene test results should be combined with hematological phenotype analysis, and prenateal diagnosis should be taken for rare thalassemia even if they＇ re unknown genotypes.