Molecular screening of β-thalassemia mutations among anaemic children and the influence of consanguinity: a hospital-based cross sectional study from South India
DOI:
https://doi.org/10.18203/2320-6012.ijrms20262632Keywords:
β-thalassemia, Anaemia, Mutation screening, Consanguinity, Molecular diagnosis, Paediatric haematologyAbstract
Background: β-thalassemia is the most common inherited haemoglobin in India, affecting 3-4% of the population. Mutations in the β-globin gene cause defective haemoglobin synthesis and chronic anaemia. Consanguineous marriage increases the risk of homozygosity for autosomal recessive disorders. Early molecular diagnosis is essential for differentiating inherited haemoglobinopathies from nutritional anaemia and for implementing preventive strategies. This study aimed to detect β-thalassemia mutations among anaemic children and evaluate the association between parental consanguinity and mutation positivity.
Methods: A hospital-based cross-sectional study was conducted between September 2021 and October 2022 among 40 children with severe anaemia, haemoglobin <8 g/dL. Demographic and clinical information, including parental consanguinity, was collected. Molecular screening for β-thalassemia mutations was performed using Real-Time PCR with the SNP Biotech Beta Thalassemia Kit on the 7500 AB systems. Statistical analyses included Chi-square test, odds ratio (OR), relative risk (RR), and 95% confidence intervals (CI).
Results: Of 40 children, 13 (32.5%) tested positive for β-thalassemia mutations. Mutation positivity was 33.3% among consanguineous families and 31.2% among non-consanguineous families. Statistical analysis showed no significant association between consanguinity and mutation positivity (χ²=0.019, p=0.890). Odds ratio analysis indicated slightly higher odds among consanguineous families (OR=1.10; 95% CI: 0.28-4.27).
Conclusions: β-thalassemia mutations were identified in a substantial proportion of severely anaemic children. Although prevalence was marginally higher in consanguineous families, comparable rates in non-consanguineous families highlight the widespread carrier burden. Molecular screening is valuable for early diagnosis, family screening, genetic counselling, and prevention of severe β-thalassemia.
References
Fibach E, Rachmilewitz EA. Pathophysiology and treatment of patients with beta-thalassemia-An update. F1000Research. 2017;6:2156.
Kattamis A, Forni GL, Aydinok Y, Viprakasit V. Changing patterns in the epidemiology of β-thalassemia. Eur J Haematol. 2020;105(6):692-703.
Modell B, Darlison M. Global epidemiology of haemoglobin disorders. Bull World Health Organ. 2008;86(6):480-7.
Rund D, Rachmilewitz E. Beta-thalassemia. N Engl J Med. 2005;353(11):1135-46.
Weatherall DJ, Clegg JB. The Thalassaemia Syndromes. 4th ed. Oxford: Blackwell Science; 2001.
Galanello R, Origa R. Beta-thalassemia: orphanet j rare dis. J Contin Educat Topics Issues. 2012;14(1):33-4.
Borgna-Pignatti C, Galanello R. Thalassemias and related disorders. Hematol Oncol Clin North Am. 2004;186:1321-44.
Hossain MS, Raheem E, Sultana TA, Ferdous S, Nahar N, Islam S, et al. Thalassemias in South Asia. Orphanet J Rare Dis. 2017;12(1):93.
Mohanty D, Colah RB, Gorakshakar AC, Patel RZ, Master DC, Mahanta J, et al. Prevalence of β-thalassemia and other haemoglobinopathies in India. J Community Genet. 2013;4(1):33-42.
Colah R, Gorakshakar A, Nadkarni A. Global burden and prevention of β-thalassemias. Expert Rev Hematol. 2010;3(1):103-117.
Kumar R, Singh K, Panigrahi I, Agarwal S. Genetic heterogeneity of beta globin mutations among Asian Indians. Mediterr J Hematol Infect Dis. 2013;5(1):e2013003.
Olivieri NF. The β-thalassemias. N Engl J Med. 1999;34(12):99-109.
Angastiniotis M, Modell B. Global epidemiology of hemoglobin disorders. Ann N Y Acad Sci. 1998;850(1):251-69.
Bittles AH. Consanguinity and its relevance to clinical genetics. Clin Genet. 2001;60(2):89-98.
Sinha S, Black ML, Agarwal S, Colah R, Das R, Ryan K, et al. Profiling β-thalassaemia mutations in India at state and regional levels: implications for genetic education, screening and counselling programmes. The HUGO J. 2009;3(1):51-62.
Old JM. Screening and genetic diagnosis of hemoglobin disorders. Blood Rev. 2003;17(1):43-53.
Madan N, Sharma S, Sood SK, Colah R. Frequency of β-thalassemia trait in India. Indian J Hum Genet. 2010;16(1):16-25.
Gorakshakar AC, Colah RB. Cascade screening for β-thalassemia. Indian J Hum Genet. 2009;15(3):93-101.
Sumedha D, Anita K. Prevalence of beta thalassemia carriers in India: A systematic review and meta-analysis. J Community Genet. 2023;14(6):527-41.
Ahmed S, Saleem M, Modell B, Petrou M. Screening extended families for genetic hemoglobin disorders in Pakistan. N Engl J Med. 2002;347(15):1162-8.
Saxena R, Phadke SR. Feasibility of thalassemia control by extended family screening in India. Indian J Med Res. 2002;11(6):31-35.
Cao A, Galanello R. Effect of consanguinity on thalassemia inheritance. Genet Med. 2010;12(2):61-76.
Cao A, Kan YW, Furbetta M. Prenatal diagnosis and screening of thalassemia. N Engl J Med. 1981;304(23):1389-92.
Lorey F, Cunningham G, Vichinsky E, et al. Universal newborn screening for hemoglobinopathies. Pediatr Hematol Oncol. 2001;18(8):501-8.
Balgir RS. The burden of hemoglobinopathies in India. Curr Sci. 2007;92(8):1096-1102.
Downloads
Published
How to Cite
Issue
Section
