+Bioline International Official Site (site up-dated regularly)

search
for

Indian Journal of Human Genetics
Medknow Publications on behalf of Indian Society of Human Genetics
ISSN: 0971-6866 EISSN: 1998-362x
Vol. 13, Num. 1, 2007, pp. 36-37

Indian Journal of Human Genetics, Vol. 13, No. 1, January-April, 2007, pp. 36-37

Letter To Editor

Mutational spectrum of thalassemias in India

Panigrahi Inusha, Marwaha R. K.

Division of Genetics, Department of Pediatrics, Advanced Pediatric Center, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh
Correspondence Address:Pediatric Genetics Advanced Pediatric Centre, Post-Graduate Institute of Medical Education and Research (PGIMER), Chandigarh - 160012, inupan@yahoo.com

Code Number: hg07008

Sir,

Thalassemias are common genetic disorders in the Indian subcontinent.^[1] Thalassemia major is the severe phenotype which requires lifelong transfusions and bone marrow transplantation is the only curative option available. Knowledge of the ethnic and geographic origin would enable molecular analysis to be tailored, keeping in view the specific mutations in that community or area. The following write-up gives a concise representation of the common thalassemia mutations in Indians.

Beta-thalassemia is clinically more significant in India, with higher incidence in certain communities. Few common mutations account for> 95% of severe beta-thalassemia cases. Concurrent presence of alpha thalassemia modifies the phenotype of beta-thalassemia. Alpha-thalassemia is not a significant problem in India because the severe alpha deletion mutations are less common in this region. The carrier rate for β -thalassemia varies from 3-17%.^[1] The alpha thalassemia carrier rate in India varies from 1 to 80%.^[1] But it is clinically less significant than β -thalassemia. Alpha thalassemia if present in β -homozygous thalassemia patients ameliorates the phenotype and majority present as thalassemia intermedia.^[2],[3] Hb E (hemoglobin E) is abnormal hemoglobin prevalent in North-Eastern States.^[4]

The five common mutations -IVS 1-5 G → C, IVS 1 -1 G → T, Codon 41/42 (- TCTT), Codon 8/9 and the 619 bp deletion account for over 90% of the mutations in β-thalassemia patients.^[5],[6] The mutations reported from different regions of India are listed in [Figure - 1].^{[7],[8],[9],[10],[11],[12]} IVS-I-5 (G → C) is the most common beta-thalassemia allele in the Indian population. Sindhis and Lohanas especially from Gujarat show high prevalence of the 619 bp deletion mutation. Rare beta-thalassemia mutations were found in 87/1233(7.06%) carriers.^[8] High frequency of the IVS-1-1 (G →T) mutation was also found in Sindhis (25.5%), Punjabi Hindus (34.7%) and Lohanas (31.2%) in the study. Jat Sikhs, a subcaste of Punjabis, revealed a very high prevalence (46%: 41/88) of the mild β++ promoter mutation -88 (C-T) in a recent study.^[13] Un-transfused patients had characteristically high Hb F (38.1-68.6%, mean 47.4%) and also Hb A2 (5.7-9.8%, mean 6.88%) values.

In alpha thalassemia the common mutations are - α^3.7 , - α^4.2 , -^SA (South African deletion)^[14] and Hb Constant Spring. The commonest mutation is - α^3.7 deletion. Hb Koya Dora is found at high frequency (10%) in certain communities of Andhra Pradesh.^[15] Hb Constant Spring and Hb Koya Dora are termination codon mutations leading to an elongated alpha chain. The a⁰ alleles (double deletion on one chromosome involving 2 alpha genes) are less common in India compared to neighboring South East Asian Countries like China and Taiwan. This is one of the reasons for alpha-thalassemia being a less important problem.

To conclude, knowledge of the native origin of affected families can help in identifying the common possible mutations and accordingly molecular analysis can be phased out.

References

1.	Higgs DR, Thein SL, Wood WG. Distribution and population genetics of the thalassemias. In: Weatherall DJ, Clegg JB, editors. The Thalassemia Syndromes. 4^th ed. Blackwell Science: Oxford; 2001. p. 237-84. Back to cited text no. 1
2.	Nadkarni A, Gorashakar AC, Lu CY, Krishnamoorthy R, Ghosh K, Colah R, et al. Molecular pathogenesis and clinical variability of [beta]-thalassemia syndromes among Indians. Am J Hematol 2001;68:75-80. Back to cited text no. 2
3.	Garewal G, Fearon CW, Warren TC, Marwaha N, Marwaha RK, Mahadik C, et al. The molecular basis of beta thalassaemia in Punjabi and Maharashtran Indians includes a multilocus aetiology involving triplicated alpha-globin loci. Br J Haematol 1994:86:372-6. Back to cited text no. 3
4.	Deka R, Reddy AP, Mukherjee BN, Das BM, Banerjee S, Roy M, et al. Hemoglobin E distribution in ten endogamous population groups of Assam, India. Hum Hered 1988;38:261-6. Back to cited text no. 4 [PUBMED]
5.	Thein SL, Hesketh C, Wallace RB, Weatherall DJ. The molecular basis of thalassaemia major and thalassaemia intermedia in Asian Indians: Application to prenatal diagnosis. Br J Haematol 1988;70:225-31. Back to cited text no. 5
6.	Varawalla NY, Old JM, Sarkar R, Venkatesan R, Weatherall DJ. The spectrum of beta-thalassaemia mutations on the Indian subcontinent: The basis for prenatal diagnosis. Br J Haematol 1991;78:242-7. Back to cited text no. 6
7.	Verma IC, Saxena R, Thomas E, Jain PK. Regional distribution of beta-thalassemia mutations in India. Hum Genet 1997;100:109-13. Back to cited text no. 7 [PUBMED] [FULLTEXT]
8.	Vaz FE, Thakur (Mahadik) CB, Banerjee MK, Gangal SG. Distribution of β-thalassemia mutations in the Indian population referred to a diagnostic center. Hemoglobin 2000;24:181-94. Back to cited text no. 8
9.	Agarwal S, Naveed M, Gupta UR, Kishore P, Agarwal SS. Characterization of beta-thalassaemia mutations in 57 beta-thalassaemia families seen at Lucknow. Indian J Med Res 1994;100:106-10. Back to cited text no. 9 [PUBMED]
10.	Bandyopadhyay A, Bandyopadhyay S, Chowdhury MD, Dasgupta UB. Major beta-globin gene mutations in eastern India and their associated haplotypes. Hum Reprod 1999;49:232-5. Back to cited text no. 10 [PUBMED] [FULLTEXT]
11.	Madan N, Sharma S, Rusia U, Sen S, Sood SK. Beta-thalassaemia mutations in northern India (Delhi). Indian J Med Res 1998;107:134-41. Back to cited text no. 11 [PUBMED]
12.	Bashyam MD, Bashyam L, Savithri GR, Gopikrishna M, Sangal V, Devi AR. Molecular genetic analyses of beta-thalassemia in South India reveals rare mutations in the beta-globin gene. J Hum Genet 2004;49:408-13. Back to cited text no. 12 [PUBMED] [FULLTEXT]
13.	Garewal G, Das R, Ahluwalia J, Marwaha RK, Varma S. Nucleotide -88 (C-T) promoter mutation is a common beta-thalassemia mutation in the Jat Sikhs of Punjab, India. Am J Hematol 2005;79:252-6. Back to cited text no. 13 [PUBMED] [FULLTEXT]
14.	Shaji RV, Eunice SE, Baidya S, Srivastava A, Chandy M. Determination of the breakpoint and molecular diagnosis of a common alpha-thalassaemia-1 deletion in the Indian population. Br J Haematol 2003;123:942-7. Back to cited text no. 14 [PUBMED]
15.	Fodde R, Losekoot M, van den Broek MH, Oldenburg M, Rashida N, Schreuder A, et al. Prevalence and molecular heterogeneity of alfa⁺ thalassemia in two tribal populations from Andhra Pradesh, India. Hum Genet 1988:80:157-60. Back to cited text no. 15 [PUBMED]

The following images related to this document are available:

Photo images

[hg07008f1.jpg]

Home	Faq	Resources	Email Bioline
© Bioline International, 1989 - 2024, Site last up-dated on 01-Sep-2022. Site created and maintained by the Reference Center on Environmental Information, CRIA, Brazil System hosted by the Google Cloud Platform, GCP, Brazil