关键词： 地中海贫血   基因诊断   产前诊断  

摘要： 目的:应用基因诊断技术对400例病人进行地中海贫血(简称地贫)基因检测,了解其基因突变的类型,旨在为临床预防地贫重症患儿的出生提供指导。方法:400个样本分别检测α-地贫及β-地贫基因型,α-地贫采用gap-PCR技术检测东南亚型缺失(--SEA)、右侧缺失(-a3.7)和左侧缺失(-a4.2),β-地贫采用聚合酶链反应(PCR)-膜反向点杂交技术(RDB)检测β-珠蛋白基因上的17个位点突变。结果:在进行地贫基因检查的400例病人中,检出α-珠蛋白基因缺失的有118例,检出β-珠蛋白基因突变者共78例,均为杂合子,检出αβ复合型地贫者6例,检出Barts水肿胎儿1例。结论:基因诊断技术能确诊地贫缺失或突变,检测绒毛、羊水或脐带血时须避免母体血污染。

关键词： 地中海贫血   MCV   MCH   基因型  

摘要： 目的了解平均红细胞体积(MCV)平均红细胞血红蛋白含量(MCH)下降的育龄人群地中海贫血基因携带情况,指导双方均携带同类型地贫基因的夫妇进行产前诊断.降低中间型和重型地贫胎儿出生率。方法对随机婚配的男女在接受婚前医学检查、孕前检查、产前检查时使用血细胞分析仪进行地贫筛查。判读标准为血常规MCV<82fl和MCH<27pg为地贫初筛阳性,初筛阳性做α、β地贫基因分析。结果 MCV MCH诊断地中海贫血敏感性为88.322%,MCV、MCH下降的育龄人群地贫基因携带率极高,双方均携带同类型地贫基因的夫妇应进行产前诊断,从而降低中间型和重型地贫胎儿出生率。结论 MCV MCH作为地中海贫血筛查方法简单、经济实用。

关键词： 重型β地中海贫血   造血干细胞移植   移植治疗   重型β-地中海贫血   β-地贫   免疫屏障   基因缺陷   红系造血  

摘要： 造血干细胞移植（HSCT）通过预处理克服受者免疫屏障，然后输注正常供体的造血干细胞（HSC），替代重型β-地中海贫血（β-地贫）受者体内基因缺陷的HSC，从而重建受者正常红系造血，是目前临床唯一可根治重型β-地贫的治疗方法。

关键词： occult HBV   hepatitis C virus   DNA   thalassemia   pediatrics  

摘要： Introduction: Thalassemia is hereditary anemia which requires lifelong transfusion as treatment, and hepatitis viral infection is one of the risks of repeated transfusions. Hepatitis B outbreaks in health-care settings are still a serious public health concern worldwide. Blood samples negative for HBsAg but positive for HBV-DNA, with or without the presence of HBV antibodies, are classified as "occult" HBV infection (OBI). This study investigated the prevalence of occult HBV infection in Egyptian thalassemic children. Methodology: Eighty patients admitted to the Faculty of Medicine, Cairo University Hospital, were involved in this prospective study. Strict inclusion criteria were set to nullify the effect of confounding variables and further minimize selection bias. The following laboratory investigations were performed: complete blood count (CBC);serum AST and ALT;albumin;bilirubin;HBsAg;HBeAg;HBcAb;HCV-RNA;and HBV-DNA. Results: All our patients had no clinical manifestation suggestive of hepatitis. Molecular biology studies revealed positivity for HCV and HBV at 25% and 32.5% respectively. Conclusion: The estimated risk of acquiring hepatitis B and C infection in children receiving multiple blood transfusions is surprisingly high. Moreover, occult hepatitis B infection is a considerably risk.

关键词： Hb Bart's   zeta-globin   ELISA   alpha-/beta-Thalassemia heterozygote   alpha-Thalassemia/HbE heterozygote  

摘要： We sought to demonstrate the ability of levels of Hb Bart's and zeta-globin chain quantified by enzyme-linked immunosorbent assay (ELISA) in detecting alpha-thalassemia in beta-thalassemia and HbE heterozygotes. We developed an in-house sandwich ELISA method using monoclonal antibodies (mAbs) to Hb Bart's and zeta-globin chain, and quantified levels of Hb Bart's and zeta-globin chain in 172 and 223 anonymous blood samples of beta-thalassemia and HbE heterozygotes, respectively. Genotypes of alpha-thalassemia 1, beta-thalassemia were identified, and HbE allele was confirmed using a newly developed multiplex allele-specific PCR. The in-house sandwich ELISA method detected Hb Bart's in 6.4% of beta-thalassemia heterozygotes, of which 5.2% showed detectable amounts of the zeta-globin chain. 15.2% of individuals heterozygous for HbE showed a detectable amount of Hb Bart's, and the zeta-globin chain was detected in 11.2% of this cohort. All samples having detectable amounts of Hb Bart's and the zeta-globin chain were verified to be SEA-type alpha-thalassemia 1. ELISA-quantified Hb Bart's and zeta-globin chain levels can be used to detect double heterozygosity of alpha- and beta-thalassemia and of alpha-thalassemia and HbE. This strategy may be useful in screening for co-existence of alpha-thalassemia in beta-thalassemia and in HbE heterozygotes, particularly in countries where alpha-, beta-thalassemia and HbE are endemic.

关键词： beta-Thalassemia   Linkage analysis   ARMS PCR   Pakistan   Mutation   Prenatal diagnosis  

摘要： beta-Thalassemia is the most common genetic disorder in Pakistan, where more than 6000 affected children are born annually, and the carrier population is around 10 million. The objective was to study beta-globin gene mutations in chorionic villous biopsy samples. Prenatal screening of 383 pregnant women between 2003 and 2010 was carried out using a panel of 13 mutation primers and amplification refractory mutations system (ARMS)-PCR. In addition, DNA sequencing was used to confirm uncharacterized mutations and in some cases fetal disease status was confirmed by linkage analysis. Families enrolled in this study represented major ethnic groups in Pakistan. Of the 13 mutations tested, three mutations accounted 71% of the total, including IVS1-5(G-C)[HBB:c.92+5G > C], codon 8/9(+G) [HBB:c.27_28insG] and del 619[NG_000007.3:g71609-72227del619]. Mutations in four uncharacterized samples were later confirmed by DNA sequencing as -88(C-T)[HBB:c.-138C > G], -90(C-T)[HBB:c.-140C > T] and codon 59(+T)[HBB:c.178_179insT]. To our knowledge, this is the first report of these mutations in Pakistan. Moreover, 19.2% fetal samples were normal and 52.3% heterozygous, whereas 26.4% were affected with thalassemia major. IVS1-5:IVS1-5 was the most common genotype in fetal samples. Prenatal diagnosis of beta-thalassemia using ARMS PCR is an efficient approach for reducing the burden of this disease in Pakistan. In addition, rare mutations reported in this study should be incorporated in the diagnostic strategy.

关键词： THALASSEMIA -- Genetic aspects   HEPCIDIN   BONE morphogenetic proteins   HEMOGLOBIN   ERYTHROPOIESIS   ERYTHROCYTE membranes  

摘要： The article discusses a study on the association of decreased hepcidin expression in murine β-thalassemia with the suppression of bone morphogenetic protein (Bmp) and Smad signaling. It informs that β-thalassemia is a genetic disorder of hemoglobin production in which ineffective erythropoiesis and anemia takes place. It also informs that different erythroid signals regulate hepcidin in normal and ineffective erythropoiesis.

关键词： 缺铁性贫血   β-地中海贫血   红细胞参数的运算公式   鉴别诊断  

摘要： 目的探讨红细胞参数的运算公式对缺铁性贫血与β-地中海贫血鉴别诊断的实用价值。方法使用全自动血细胞分析仪对160例缺铁性贫血和172例β-地中海贫血患者的红细胞相关参数进行检测,以文献报道的5个红细胞参数的运算公式作为缺铁性贫血与β-地中海贫血的鉴别指标,分析它们的灵敏度、特异度、假阳性率、假阴性率、阳性预测值、阴性预测值、约登指数、阳性似然比、阴性似然比、对应的ROC曲线以及曲线下面积。结果在诊断IDA时,MI、S&BI、SI、和EI灵敏度在72.5%-81.88%,但特异度较低,在22.09%-26.74%之间;S&LI特异度为62.79%,但灵敏度仅为9.38%。在诊断β-地中海贫血时结果相反。各红细胞参数运算公式的约登指数和阳性似然比都较低。ROC曲线下面积最高的S&LI仅为0.753。结论上述5个红细胞参数运算公式对IDA和β-TT的鉴别诊断效能不高。

关键词： 重型β地中海贫血   BCL11A基因   γ基因   HbF  

摘要： 目的探讨重型β地中海贫血患者(thalassemia major,TM)BCL11A表达特点及其与临床表现的关系。方法正常人和TM患者各24例,分离外周血单个核细胞,实时荧光定量聚合酶链反应(quantitative real time polymer-ase chain reaction,qRT-PCR)法检测BCL11A、γ基因mRNA表达水平,同时检测血常规血红蛋白(hemoglobin,Hb)、血红蛋白分析仪检测胎儿血红蛋白(fetal hemoglobin,HbF),并行相关性检验。结果 TM患者的HbF、γmRNA水平显著高于正常人群(13.7%±13.6%vs 0.28%±0.15%,P<0.001;2479%±279%vs 10.61%±0.41%,P<0.001),2组BCL11A基因mRNA水平无统计学差异(0.73%±0.26%vs 0.77%±0.22%,P=0.590)。TM患者中25%(6例)的患者HbF正常,与HbF升高者比较,其γmRNA水平要低(62.10%±16.49%vs 3285.2%±2792.2%,P<0.001),但BCL11A mRNA水平无统计学差异(0.78%±0.21%vs 0.72%±0.28%,P=0.704)。TM患者BCL11A mRNA水平与首次输血年龄无显著相关(r=0.201,P=0.345)。结论 BCL11A不参与TM患者的γ基因的开放和HbF代偿性增加。