孕早期胎儿地中海贫血基因型与血液学表型和产前诊断适应证的遗传研究

Application of Invasive Prenatal Diagnosis for Fetal Thalassemia Genotype and Haematological Phenotype in Early Pregnancy

目的:探讨孕早期侵入性产前诊断分析地中海贫血夫妇的基因型分布与血液临床表型和产前高危因素之间的遗传关联,以更好地进行地中海贫血高风险夫妇孕早期产前诊断和遗传咨询。方法:通过对606例高风险夫妇行腹部绒毛活检术(TA-CVS)进行基因型结果分析,并依据不同的基因组合对其血液学指标血红蛋白(Hb)、平均红细胞容积(MCV)、平均红细胞血红蛋白(MCH)和血红蛋白A2(HbA2)进行比较,分析产前诊断适应证的高危风险因素与胎儿基因型临床表型结果的关系。结果:①606例绒毛标本中,地中海贫血的胎儿标本463例,其中α地中海贫血携带者共检测出基因型16种,以常见基因型--SEA/αα(东南亚缺失)为主(26.3%)。②胎儿α地中海贫血基因的Bart's和HbH病临床表型其父母血液参数呈现特点为中度且小细胞低色素贫血,且Bart's胎儿其父母血液学表型MCV、MCH、Hb水平均较HbH病低(P<0.05);β双重杂合子或纯合子的血液学特点为小细胞低色素性贫血,α复合β地中海贫血和β地中海贫血杂合子血液学参数特点为轻度降低或正常,HbA2值升高或正常,且β双重杂合子或纯合子父母双方的MCV、MCH、Hb水平均显著低于相应的α复合β地中海贫血和β地中海贫血杂合子(P<0.05)。③产前诊断适应证中夫妇双方高风险的高危因素中Bart's和HbH所占例数高于高龄超声异常、不良孕产史、染色体异常和重型Bart's生育史产前诊断适应证。结论:广西地区胎儿地中海贫血中以α地中海贫血东南亚缺失型发病率为主;各种胎儿基因型结果其父母血液学参数变异性较大,夫妇双方地中海贫血高风险的高危因素致地中海贫血患儿的风险系数较高,临床上应结合患者的血液学表型和产前诊断的危险因素进行判断,以避免漏诊。

Objective：Through the invasive prenatal diagnosis of genetic association between the distributions of genotypes and haematological phenotypes in thalassemia couples and prenatal risk factors in early pregnancy,contributing to the management of couples at high-risk in thalassemia in early pregnancy. Methods：Genotype analyses were performed in 606 cases with high risk who underwent trans-abdominal chorionic villus biopsy （ TA-CVS）, and the correlation with the hematology indexes including average hemoglobin （Hb）, red blood cell volume（MCV）, average red blood cell hemoglobin （MCH） and hemoglobin A2 （HbA2） were compared, with the aim to figure out the correlation between the high risk factors for prenatal diagnosis indication and fetal genotypes. Results：（1）There were 463 cases of fetal thalassemia in the 606 chorionic villus samples. 16 genotypes were detected in α-thalassemia carriers, and the --^SEA/αα （Southeast Asia） （26. 3% ）was the most common genotype. （2）The parents of fetus with Bart＇s and HbH phenotype were usually characterized by moderate hypochromic microcytic anemia., and those with Bart＇s phenotype had lower MCV, MCH, Hb levels than those with HbH phenotype （P 〈 0.05）. Carriers of β double heterozygous or homozygous were characterized by hypochromic microcytic anemia. Carriers of αβ compound and βheterozygous were characterized by mild lower or normal values of hematological parameters. （3）Among the high risk factors for prenatal diagnosis indications, the proportion of Bart＇s and HbH phenotypes was higher than ultrasound abnormalities, abnormal pregnancy history, chromosomal abnormalities and birth history of severe Bart＇s phenotype. Conclusions： In Guangxi autonmous region, alpha thalassemia with -- ^SEA/αα was the most common genotype. In term of a certain fetal genotype,the hematological characteristics of the parents varied apparently,and the risk index for fetal thalassemia became higher when the parents both carried high risk factors of thalassemia. To avoid missed diagnosis,it was important to make a comprehensive judgment based on haematological phenotype and risk factor in prenatal diagnosis.