Aims: Thalassemia is a common autosomal recessive blood disorder, which is most prevalent in South East Asian and Mediterranean populations. It is considered as a major health burden in the Indian population. The aims of the present study were to investigate the common, as well as uncommon, mutations responsible for thalassemia in the Bengali population. Methods: The Bengali state was divided into four sampling zones. Mutation detection was done using Sanger sequencing of the HBB gene. Results: A total of 14 different mutations were observed, including rare mutations IVS1-130(G>C), IVS1-129(A>C), -90(T>C), CD16(-C), -30(T>C), CD15(-T), and a novel mutation CD53(C>T). The frequencies of IVS1-5(G>C) and CD26(G>A) mutations were higher than other mutations. There were also some silent polymorphisms found in the studied group, CD3(T>C), CD10(C>A), IVSII-16(G>C), IVSII-74(T>G), -42(C>G). Conclusion: The present study is the first attempt to screen for β-thalassemia-causing mutations by direct sequencing in different districts of West Bengal. The information obtained from the present study may be helpful for thalassemia management and prenatal mutation detection.
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References
1.
AchoubiN, AsgharM, SaraswathyKN, MurryB (2012) Prevalence of β-thalassemia and hemoglobin E in two migrant populations of Manipur, North East India. Genet Test Mol Biomarkers, 16:1195-1200.
2.
AgarwalS, TamhankarPM, KumarR, DalalA (2009) Clinical and haematological features in a compound heterozygote (HBB:c.92 + 5G > C/HBB:c.93-2A > C) case of thalassaemia major. Int J Lab Hematol, 32:369-372.
3.
AyubMI, MoosaMM, SarwardiG, et al. (2010) Mutation analysis of the HBB gene in selected Bangladeshi b-thalassemic individuals: presence of rare mutations. Genet Test Mol Biomarkers, 14:299-302.
4.
BalgirRS (2005) Spectrum of hemoglobinopathies in the State of Orissa, India: a ten years cohort study. J Assoc Physicians India, 53:1021-1026.
5.
BandyopadhyayA, BandyopadhyayS, BasakJ, et al. (2004) Profile of beta-thalassemia in eastern India and its prenatal diagnosis. Prenat Diagn, 24:992-996.
6.
BandyopadhyayA, BandyopadhyayS, DasguptaUB, et al. (2001) Detection of a rare splice acceptor site mutation (IVS I nt 130 G→C) of the beta globin gene in 3 patients of Eastern India. Am J Hematol, 67:149.
7.
BandyopadhyayU, KunduD, SinhaA, et al. (2013) Conservative management of beta-thalassemia major cases in the sub-division level hospital of rural West Bengal, India. J Nat Sci Biol Med, 4:108-112.
8.
BhukhanvalaDS, ItaliaK, SawantP, et al. (2013) Molecular characterization of β-thalassemia in four communities in South Gujarat-codon 30 (G>A) a predominant mutation in the Kachhiya Patel community. Ann Hematol, 92:1473-1476.
9.
BlackML, SinhaS, AgarwalS, et al. (2010) A descriptive profile of β thalassaemia mutations in India, Pakistan and Sri Lanka. J Community Genet, 1:149-157.
10.
CaiSP, ZhangJZ, DohertyM, KanYW (1989) A new TATA box mutation detected at prenatal diagnosis for β-thalassemia. Am J Hum Genet, 45:112-114.
11.
ChandrashekarV, SoniM (2011) Hemoglobin disorders in South India. ISRN Hematol, 2011:1-6.
12.
ColahR, GorakshakarA, PhanasgaonkarS, et al. (2010) Epidemiology of beta-thalassaemia in Western India: mapping the frequencies and mutations in sub-regions of Maharashtra and Gujarat. Br J Haematol, 149:739-747.
13.
DatkhileKD, PatilMN, VavhalRD, KhamkarTS (2015) The spectrum of b-globin gene mutations in thalassemia patients of South-Western Maharashtra: a cross sectional study. JKIMSU, 4:49-58.
14.
EdisonES, ShajiRV, DeviSG, et al. (2008). Analysis of beta globin mutations in the Indian population, presence of rare and novel mutations and region-wise heterogeneity. Clin Genet, 73:331-337.
15.
FucharoenS, FucharoenG, AtaK, et al. (1990) Molecular characterization and nonradioactive detection of beta- thalassemia in Malaysia. Acta Haematol, 84:82-88.
16.
GarewalG, DasR (2003) Spectrum of β-thalassemia mutations in Punjabis. Int J Hum Genet, 3:217-219.
17.
GhoshN, ChakrabartiI, ChakrabortyM, GoswamiBK (2013) A community based pilot study on prevalence of hemoglobinopathies among the antenatal women in a rural area of Darjeeling district,West Bengal. Int J Med Public Health, 3:107-110.
18.
GorakshakarA, NadkarniA, PhanasgaonkarS, et al. (2005) Detection of two rare β-thalassemia mutations [-90 (C→T) and CD 26 (C→T)] among Indians. Indian J Hum Genet, 11:76-79.
19.
GrowK, VashistM, AbrolP, et al. (2014) Beta thalassemia in India: current status and the challenges ahead. Int J Pharm Pharm Sci, 6:28-33.
20.
GuptaA, HattoriY, GuptaUR, et al. (2003) Molecular genetic testing of beta thalassemia patients of Indian origin and a novel 8bp deletion mutation at codons 36/37/38/39. Genet Test, 7:163-168.
21.
GuptaA, SarwaiS, PathakN, AgarwalS (2008) Beta-globin gene mutations in India and their linkage to β-haplotypes. Int J Hum Genet, 8:237-241.
KukretiR, DashD, VKE, et al. (2002) Spectrum of beta-thalassemia mutations and their association with allelic sequence polymorphisms at the beta-globin gene cluster in an Eastern Indian population. Am J Hematol, 70:269-277.
24.
KulkarniGD, KulkarniSS, KadakolGS, et al. (2012) Molecular basis of b-thalassemia in Karnataka, India. Genet Test Mol Biomarkers, 16:138-141.
25.
MadanN, SharmaS, SoodSK, et al. (2010) Frequency of β-thalassemia trait and other hemoglobinopathies in northern and western India. Indian J Hum Genet, 16:16-25.
26.
MeenaLP, KumarK, SinghVK, et al. (2013) Study of mutations in β-thalassemia trait among blood donors in Eastern Uttar Pradesh. J Clin Diagn Res, 7:1394-1396.
27.
NadkarniA, SakaguchiT, GorakshakarA, et al. (2004) An interplay of alleviating mutations in the clinical phenotype of β-thalassaemia intermedia. Clin Lab Haematol, 26:419-422.
28.
NagarR, SinhaS, RamanR (2015) Genotype-phenotype correlation and report of novel mutations in β-globin gene in thalassemia patients. Blood Cells Mol Dis, 55:10-14.
29.
PanigrahiI, MarwahaRK (2007) Mutational spectrum of thalassemias in India. Indian J Hum Genet, 13:36-37.
30.
PanjaA, ChowdhuryP, BasuA (2016a) Hb Midnapore [β53(D4)Ala→Val; HBB: c.161C > T]: A novel hemoglobin variant with a structural abnormality associated with IVS-I-5 (G > C) (HBB: c.92 + 5G > C) found in a Bengali Indian family. Hemoglobin [Epub ahead of print] http://dx.doi.org/10.1080/03630269.2016.1243555
31.
PatraPK, ChauhanVS, KhodiarPK, et al. (2011) Screening for the sickle cell gene in Chhattisgarh state, India: an approach to a major public health problem. J Community Genet, 2:147-151.
32.
PatrinosGP, GiardineB, RiemerC, et al. (2004) Improvements in the HbVar database of human hemoglobin variants and thalassemia mutations for population and sequence variation studies. Nucleic Acids Res, 32:537-541.
33.
SahooSS, BiswalS, DixitM (2013) Distinctive mutation spectrum of the HBB gene in an urban eastern Indian population. Hemoglobin, 38:33-38.
34.
SinhaS, BlackML, AgarwalS, et al. (2009) Profiling β-thalassaemia mutations in India at state and regional levels: implications for genetic education, screening and counselling programmes. Hugo J, 3:51-62.
35.
SultanaGNN, BegumR, AkhterH, et al. (2016) The complete spectrum of beta (β) thalassemia mutations in Bangladeshi population. Austin Biomarkers Diagn, 3:1-6.
36.
VermaIC, SaxenaR, ThomasE, JainPK (1997) Regional distribution of b-thalassemia mutations in India. Hum Genet, 100:109-113.
37.
WangS, ZhangR, XiangG, et al. (2015) Mutation screening for thalassaemia in the Jino ethnic minority population of Yunnan Province, Southwest China. BMJ Open, 5:1-7.
