Nationwide carrier detection and molecular characterization of β-thalassemia and hemoglobin E variants in Bangladeshi population

Orphanet Journal of Rare Diseases

Waqar Ahmed Khan¹  Hossain Uddin Shekhar²  Mujahida Rahman³  Syeda Kashfi Qadri⁴  Khaleda Islam⁵  Farjana Akther Noor⁶  Syed Saleheen Qadri⁶  Golam Sarower Bhuyan⁶  Nusrat Sultana⁶  Firdausi Qadri⁶  Mohabbat Hossain⁶  Md Tarikul Islam⁶  Kaiissar Mannoor⁶  Suprovath Kumar Sarker⁶ 

[1]Department of Biochemistry and Molecular Biology, Dhaka Shishu Hospital

[2]Department of Biochemistry and Molecular Biology, University of Dhaka

[3]Department of Hematology, Bangabandhu Sheikh Mujib Medical University

[4]Department of Pediatric Medicine, KK Women’s and Children’s Hospital

[5]Directorate General of Health Services, MoHFW, Government of Bangladesh

[6]Laboratory of Genetics and Genomics, Institute for Developing Science and Health Initiatives

关键词: ß-thalassemia;    Carrier frequency;    HRM curve analysis;    Detection accuracy;    Novel mutation;    National policy;   

DOI  :  10.1186/s13023-020-1294-z

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown