当前位置: X-MOL 学术Orphanet J. Rare Dis. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Nationwide carrier detection and molecular characterization of β-thalassemia and hemoglobin E variants in Bangladeshi population.
Orphanet Journal of Rare Diseases ( IF 3.7 ) Pub Date : 2020-01-15 , DOI: 10.1186/s13023-020-1294-z
Farjana Akther Noor 1, 2 , Nusrat Sultana 1, 3 , Golam Sarower Bhuyan 1 , Md Tarikul Islam 1 , Mohabbat Hossain 1 , Suprovath Kumar Sarker 1 , Khaleda Islam 4 , Waqar Ahmed Khan 5 , Mujahida Rahman 6 , Syeda Kashfi Qadri 7 , Hossain Uddin Shekhar 2 , Firdausi Qadri 1, 8 , Syed Saleheen Qadri 1 , Kaiissar Mannoor 1
Affiliation  

BACKGROUND ß-thalassemia is one of the most common inherited blood disorders in the world and a major deterrent to the public health of Bangladesh. The management of thalassemia patients requires lifelong frequent blood transfusion and the available treatment options are unsatisfactory. A national policy on thalassemia prevention is mandatory in Bangladesh. However, precise and up-to-date information on the frequency of ß-thalassemia carriers are missing due to lack of accurate diagnostic approaches, limited access to information and absence of national screening program. This study aims to determine the nationwide carrier frequency of hemoglobin E (HbE) and β- thalassemia and mutation spectrum among the carriers using molecular, hematological and biochemical methods. METHODS The study enrolled a total of 1877 individuals (60.1% male and 39.9% female) aged between 18 and 35 years. Total sample size and its division-wise breakdown were calculated in proportion to national and division-wise population. Venous blood was collected and subjected to CBC analysis and Hb-electrophoresis for each participant. Serum ferritin was measured to detect coexistence of iron deficiency anemia with thalassemia carrier. DNA-based High Resolution Melting (HRM) curve analysis was performed for confirmation of carrier status by mutation detection. RESULTS Of 11.89% (95% CI, 10.43-13.35) carriers of β-globin gene mutations, 8.68% (95% CI, 7.41-9.95) had HbE trait (ETT) and 2.24% (95% CI, 1.57-2.91) had beta-thalassemia trait (BTT). Among eight divisions, Rangpur had the highest carrier frequency of 27.1% (ETT-25%, BTT-2.1%), whereas Khulna had the lowest frequency of 4.2% (ETT-4.2% only). Moreover, α- thalassemia, HbD trait, HbE disease, hereditary persistence of HbF were detected in 0.11, 0.16, 0.43 and 0.16% participants, respectively. HRM could identify two individuals with reported pathogenic mutations in both alleles who were erroneously interpreted as carriers by hematological indices. Finally, a total of nine different mutations including a novel mutation (c.151A > G) were detected in the β-globin gene. CONCLUSIONS Since carrier frequency for both HbE and β-thalassemia is alarmingly high in Bangladesh, a nationwide awareness and prevention program should be made mandatory to halt the current deteriorating situations. Mutation-based confirmation is highly recommended for the inconclusive cases with conventional carrier screening methods to avoid any faulty detection of thalassemia carriers.

中文翻译:

孟加拉国人口的全国性携带者检测和β地中海贫血和血红蛋白E变异的分子表征。

背景ß地中海贫血是世界上最常见的遗传性血液疾病之一,对孟加拉国的公共卫生具有重大威慑作用。地中海贫血患者的治疗需要终生频繁输血,而可用的治疗方案也不尽人意。孟加拉国必须制定预防地中海贫血的国家政策。但是,由于缺乏准确的诊断方法,信息获取受限以及缺乏国家筛查计划,因此缺少有关β地中海贫血携带者频率的准确和最新信息。本研究旨在通过分子,血液学和生化方法确定全国血红蛋白E(HbE)和β-地中海贫血的携带者频率以及携带者之间的突变谱。方法该研究共招募了1877名个体(男性占60.1%,39岁。9%的女性)年龄在18至35岁之间。总样本量及其按国家和地区划分的人口比例进行了细分。收集静脉血,并对每个参与者进行CBC分析和Hb电泳。测量血清铁蛋白以检测铁缺乏性贫血与地中海贫血携带者的共存。进行了基于DNA的高分辨率熔解(HRM)曲线分析,以通过突变检测确认载体状态。结果在11.89%(95%CI,10.43-13.35)的β-珠蛋白基因突变携带者中,8.68%(95%CI,7.41-9.95)具有HbE特质(ETT)和2.24%(95%CI,1.57-2.91)患有β地中海贫血特征(BTT)。在八个部门中,朗布尔的最高载波频率为27.1%(ETT-25%,BTT-2.1%),而库尔纳的最低载波频率为4.2%(仅ETT-4.2%)。此外,分别在0.11、0.16、0.43和0.16%的参与者中检测到α-地中海贫血,HbD性状,HbE疾病,HbF的遗传持久性。HRM可以识别两个等位基因中报告有致病性突变的个体,这些个体被血液学指标错误地解释为携带者。最后,在β-珠蛋白基因中总共检测到九种不同的突变,包括新突变(c.151A> G)。结论由于孟加拉国HbE和β地中海贫血的载频高得惊人,因此必须强制执行一项全国性的预防计划,以制止当前不断恶化的局势。强烈建议使用常规携带者筛查方法对不确定的病例进行基于突变的确认,以避免地中海贫血携带者的任何错误检测。分别在0.11、0.16、0.43和0.16%的参与者中检测到HbF的遗传持久性。HRM可以识别两个等位基因中报告有致病性突变的个体,这些个体被血液学指标错误地解释为携带者。最后,在β-珠蛋白基因中总共检测到九种不同的突变,包括新突变(c.151A> G)。结论由于孟加拉国HbE和β地中海贫血的载频高得惊人,因此必须强制执行一项全国性的预防计划,以制止当前不断恶化的局势。强烈建议使用常规携带者筛查方法对不确定的病例进行基于突变的确认,以避免地中海贫血携带者的任何错误检测。分别在0.11、0.16、0.43和0.16%的参与者中检测到HbF的遗传持久性。HRM可以识别两个等位基因中报告有致病性突变的个体,这些个体被血液学指标错误地解释为携带者。最后,在β-珠蛋白基因中总共检测到九种不同的突变,包括新突变(c.151A> G)。结论由于孟加拉国HbE和β地中海贫血的载频高得惊人,因此必须强制执行一项全国性的预防计划,以制止当前不断恶化的局势。强烈建议使用常规携带者筛查方法对不确定的病例进行基于突变的确认,以避免地中海贫血携带者的任何错误检测。分别。HRM可以识别两个等位基因中报告有致病突变的个体,这些个体被血液学指标错误地解释为携带者。最后,在β-珠蛋白基因中总共检测到九种不同的突变,包括新突变(c.151A> G)。结论由于孟加拉国HbE和β地中海贫血的载频高得惊人,因此必须强制执行一项全国性的预防计划,以制止当前不断恶化的局势。强烈建议使用常规携带者筛查方法对不确定的病例进行基于突变的确认,以避免地中海贫血携带者的任何错误检测。分别。HRM可以识别两个等位基因中报告有致病性突变的个体,这些个体被血液学指标错误地解释为携带者。最后,在β-珠蛋白基因中总共检测到九种不同的突变,包括新突变(c.151A> G)。结论由于孟加拉国HbE和β地中海贫血的载频高得惊人,因此必须强制执行一项全国性的预防和预防计划,以制止当前不断恶化的局势。强烈建议使用常规携带者筛查方法对不确定的病例进行基于突变的确认,以避免地中海贫血携带者的任何错误检测。最后,在β-珠蛋白基因中总共检测到九种不同的突变,包括新突变(c.151A> G)。结论由于孟加拉国HbE和β地中海贫血的载频高得惊人,因此必须强制执行一项全国性的预防计划,以制止当前不断恶化的局势。强烈建议使用常规携带者筛查方法对不确定的病例进行基于突变的确认,以避免地中海贫血携带者的任何错误检测。最后,在β-珠蛋白基因中总共检测到九种不同的突变,包括新突变(c.151A> G)。结论由于孟加拉国HbE和β地中海贫血的载频高得惊人,因此必须强制执行一项全国性的预防计划,以制止当前不断恶化的局势。强烈建议使用常规携带者筛查方法对不确定的病例进行基于突变的确认,以避免地中海贫血携带者的任何错误检测。
更新日期:2020-01-15
down
wechat
bug