Beta thalassemia is caused by a mutation in the human beta globin gene. More than 400 causative mutations have been characterized in the Hemoglobin Subunit Beta (HBB) gene. These causative mutations are present in the beta globin gene or the regulatory region. Though more than 400 causative mutations of HBB region have been described, rare and novel mutations are being reported in studies indicating the need for characterization of mutations in all regions and information regarding the same should be made available for successful implementation of prenatal diagnosis. The study aims to characterize the spectrum of beta thalassemia mutations in beta thalassemia heterozygous among residents of Chennai. A total of 5,207 cases were screened for beta thalassemia heterozygous by HPLC method. 387 beta thalassemia heterozygous identified by HPLC method were subjected to molecular DNA analysis by ARMS PCR technique and DNA Sanger sequencing for the characterization of causative beta thalassemia mutations. In the present study molecular characterization of beta thalassemia mutations revealed 30 different mutations with a high prevalence of IVS 1-5 (G-C) mutation, five new rare mutations viz., IVS II-1 (G>T), CD 37 TGG-TGA, IVS II 781 (C-G), CD114 CTG-CCG and Poly A (A-G) were diagnosed and reported first in India. One novel beta thalassemia mutation HBB.c319DelC was detected in the study. The diagnostic outcome of detecting the causative mutations for beta thalassemia imposes strong resources for developing easy and cheaper methods for prenatal diagnosis which will reduce the burden of disease.
Citation: Bhuvana Selvaraj, Ganesan Subramanian, Senthil Kumar Ramanathan, Sangeetha Soundararajan, Shettu Narayanasamy. Studies on molecular spectrum of beta thalassemia among residents of Chennai[J]. AIMS Molecular Science, 2022, 9(3): 107-135. doi: 10.3934/molsci.2022007
Beta thalassemia is caused by a mutation in the human beta globin gene. More than 400 causative mutations have been characterized in the Hemoglobin Subunit Beta (HBB) gene. These causative mutations are present in the beta globin gene or the regulatory region. Though more than 400 causative mutations of HBB region have been described, rare and novel mutations are being reported in studies indicating the need for characterization of mutations in all regions and information regarding the same should be made available for successful implementation of prenatal diagnosis. The study aims to characterize the spectrum of beta thalassemia mutations in beta thalassemia heterozygous among residents of Chennai. A total of 5,207 cases were screened for beta thalassemia heterozygous by HPLC method. 387 beta thalassemia heterozygous identified by HPLC method were subjected to molecular DNA analysis by ARMS PCR technique and DNA Sanger sequencing for the characterization of causative beta thalassemia mutations. In the present study molecular characterization of beta thalassemia mutations revealed 30 different mutations with a high prevalence of IVS 1-5 (G-C) mutation, five new rare mutations viz., IVS II-1 (G>T), CD 37 TGG-TGA, IVS II 781 (C-G), CD114 CTG-CCG and Poly A (A-G) were diagnosed and reported first in India. One novel beta thalassemia mutation HBB.c319DelC was detected in the study. The diagnostic outcome of detecting the causative mutations for beta thalassemia imposes strong resources for developing easy and cheaper methods for prenatal diagnosis which will reduce the burden of disease.
| [1] | Bain BJ (2006) Haemoglobinopathy Diagnosis. Oxford, UK: Blackwell 1-314. https://doi.org/10.1002/9780470988787 |
| [2] | Weatherall DJ, Clegg JB (2001) The Thalassemia Syndromes. Oxford: Blackwell Science Ltd 847. https://doi.org/10.1002/9780470696705 |
| [3] |
Steinberg MH, Forget BG, Higgs DR, et al. (2009) Disorders of hemoglobin: genetics, pathophysiology, and clinical management.Cambridge University Press. https://doi.org/10.1017/CBO9780511596582 
|
| [4] |
Chaudhary S, Dhawan D, Sojitra N, et al. (2017) Whole gene sequencing based screening approach to detect β-thalassemia mutations. Biology and Medicine 9: 2. https://doi.org/10.4172/0974-8369.1000383
|
| [5] | Angastiniotis M, Model lB, Englezos P, et al. (1995) Prevention and controlof haemoglobinopathies. Bulletin of the World Health Organization 73: 375. |
| [6] |
Colah R, Gorakshakar A, Nadkarni A (2010) Global burden, distribution and preventionof β-thalassemias and hemoglobin E disorders. Expert Review of Hematology 3: 103-117. https://doi.org/10.1586/ehm.09.74
|
| [7] | WHO/TIF Meeting on the Management of Haemoglobin Disorders (2007:Nicosia,Cyprus), World Health Organization & Thalassaemia International Federation.Management of haemoglobin disorders: report of a joint WHO-TIF meeting, Nicosia, Cyprus, 16-18 November 2007. World Health Organization (2008) . https://apps.who.int/iris/handle/10665/43969 |
| [8] |
Ghosh K, Colah R, Manglani M, et al. (2014) Guidelines for screening, diagnosis and management of hemoglobinopathies. Indian journal of human genetics 20: 101. https://doi.org/10.4103/0971-6866.142841
|
| [9] | Krishnamurthy BN, Niveditha SR, Shankar P (2016) Frequency of Beta thalassemia 651 trait in pediatric age group in a tertiary care hospital in south India. Annals of Applied Bio Sciences 3: A143-150. |
| [10] | Vehapoglu A, Ozgurhan G, Demir AD, et al. (2014) Hematological indices for differential diagnosis of Beta thalassemia trait and iron deficiency anemia. Anemia 2014 . https://doi.org/10.1155/2014/576738 |
| [11] | Bhuvana S, Rajan S (2016) Studies on Beta Thalassemia and other Hemoglobinopathies in Metropolitan City of Chennai, Tamil Nadu, India. International Journal on Biological Sciences 7: 7-19. |
| [12] |
Weatherall DJ (2010) The inherited diseases of hemoglobin are an emerging global health burden. Blood 115: 4331-4336. https://doi.org/10.1182/blood-2010-01-251348
|
| [13] |
Vichinsky EP, MacKlin EA, Waye JS, et al. (2005) Changes in the epidemiology of thalassemia in North America: a new minority disease. Pediatrics 116: 818-825. https://doi.org/10.1542/peds.2005-0843
|
| [14] | PRB: Population Reference Bureau-World Population Data Sheet (2019). Available from: https://www.prb.org/worldpopdata/ |
| [15] | Colah RB, Gorakshakar A (2014) Control of thalassemia in India. Thalassemia Reports . https://doi.org/10.4081/thal.2014.1955 |
| [16] |
Goswami BK, Pramanik R, Chakrabarty S, et al. (2014) Spectrum of hemoglobin variants in the population of Northern region of WestBengal: An ethnogenetic proposition. Journal of family medicine and primary care 3: 219. https://doi.org/10.4103/2249-4863.141614
|
| [17] |
Shrivastav A, Patel U, Joshi JR, et al. (2013) Study of hemoglobinopathies and Hb variants in population of Western India using HPLC: A report of 7,000 cases. Journal of Applied Hematology 4: 104. https://doi.org/10.4103/1658-5127.123308
|
| [18] | DeBenoist B, Cogswell M, Egli I, et al. Worldwide prevalence of anaemia 1993–2005, WHO Global Database of anaemia (2008). |
| [19] | Yousafzai YM, Wahid QUA, Khan S, et al. (2019) Co-existing iron deficiency/overload in beta-thalassemia trait. The Journal of the Pakistan Medical Association 69: 806-810. |
| [20] | Mohanty D, Colah R Laboratory Manual for screening diagnosis and molecular analysis of hemoglobinopathies and red cell enzymopathies (2008). |
| [21] | NCBI BLAST. Available from: https://blast.ncbi.nlm.nih.gov & https://www.ncbi.nlm.nih.gov/snp/. |
| [22] | Tamil Nadu Population Sex Ratio in Tamil Nadu Literacy rate data 2011-2022 (2022). Available from: https://www.census2011.co.in/ |
| [23] |
Varawalla NY, Old JM, Sarkar R, et al. (1991) The spectrum of β-thalassaemia mutations on the Indian subcontinent: the basis for prenatal diagnosis. British journal of haematology 78: 242-247. https://doi.org/10.1111/j.1365-2141.1991.tb04423.x
|
| [24] |
Venkatesan R, Sarkar R, Old JM (1992) β-Thalassaemia mutations and their linkage to β-haplotypes in Tamil Nadu in Southern India. Clinical genetics 42: 251-256. https://doi.org/10.1111/j.1399-0004.1992.tb03250.x
|
| [25] |
Verma IC (2000) Burden of genetic disorders in India. The Indian Journalof Pediatrics 67: 893-898. https://doi.org/10.1007/bf02723953
|
| [26] |
Colah R, Gorakshakar A, Nadkarni A, et al. (2009) Regional heterogeneity of β-thalassemia mutations in the multi ethnic Indian population. Blood Cells, Molecules, and Diseases 42: 241-246. https://doi.org/10.1016/j.bcmd.2008.12.006
|
| [27] |
Colah R, Gorakshakar A, Phanasgaonkar S, et al. (2010) Epidemiology of β-thalassaemia inWestern India: mapping the frequencies and mutations in sub-regions of Maharashtra and Gujarat. British journal of haematology 149: 739-747. https://doi.org/10.1111/j.1365-2141.2010.08131.x
|
| [28] |
Edison ES, Shaji RV, Devi SG, et al. (2008) Analysis of β globin mutations in the Indian population: Presence of rare and novel mutations and region-wise heterogeneity. Clinical genetics 73: 331-337. https://doi.org/10.1111/j.1399-0004.2008.00973.x
|
| [29] |
Bashyam MD, Bashyam L, Savithri GR, et al. (2004) Molecular genetic analyses of β-thalassemia in South India reveals rare mutations in the β-globin gene. Journal of human genetics 49: 408-413. https://doi.org/10.1007/s10038-004-0169-9
|
| [30] | Suresh Babu TV, Shantaram M (2016) An incidence of β-thalassemia in South India–a review. Int J Res Pharm Biosci 3: 1-6. |
| [31] |
Sinha S, Black ML, Agarwal S, et al. (2009) Profiling β-thalassaemia mutations in India at state and regional levels: implications for geneticeducation, screening and counselling programmes. The HUGO journal 3: 51. https://doi.org/10.1007/s11568-010-9132-3
|
| [32] | Varawalla NY, Fitches AC, Old JM (1992) Analysis of β-globin gene haplotypes in Asian Indians: origin and spread of β-thalassaemia on the Indian subcontinent. Humangenetics 90: 443-449. https://doi.org/10.1007/BF00220475 |
| [33] |
Bhardwaj U, Zhang YH, Lorey F, et al. (2005) Molecular genetic confirmatory testing from newborn screening samples for the common African-American, Asian Indian, Southeast Asian,and Chinese β-thalassemia mutations. American journal of hematology 78: 249-255. https://doi.org/10.1002/ajh.20269
|
| [34] | Usman M, Moinuddin M, Ghani R, et al. Screening of five common beta thalassemia mutations in the Pakistani population: a basis for prenatal diagnosis. Sultan Qaboos University Medical Journal (2009)9: 305. |
| [35] | Shakeel M, Arif M, Rehman SU, et al. (2016) Investigation of molecular heterogeneity of β-thalassemia disorder in District Charsadda of Pakistan. Pakistan journal of medical sciences 32: 491. https://doi.org/10.12669/pjms.322.9415 |
| [36] |
Mahdieh N, Rabbani B (2016) Beta thalassemia in 31,734 cases with HBB gene mutationspathogenic and structural analysis of the common mutations; Iran as the crossroads of the Middle East. Blood reviews 30: 493-508. https://doi.org/10.1016/j.blre.2016.07.001
|
| [37] |
Alotibi RS, Alharbi, Aljuhani B, et al. (2019) The frequency and spectrum of HBB gene mutation in β-Thalassemia patients in Saudi Arabia. Journal of Natural Science, Biology and Medicine 10: 97. https://doi.org/10.4103/jnsbm.JNSBM_62_18
|
| [38] |
Alaithan MA, AbdulAzeez S, Borgio JF (2018) A comprehensive review of theprevalence of beta globin gene variations and the co-inheritance of related gene variants in Saudi Arabians with beta-thalassemia. Saudi medical journal 39: 329. https://doi.org/10.15537/smj.2018.4.21360
|
| [39] |
Al-Allawi NA, Al-Mousawi BM, Badi AI, et al. (2013) The spectrum of β-thalassemia mutations in Baghdad, Central Iraq. Hemoglobin 37: 444-453. https://doi.org/10.3109/03630269.2013.810641
|
| [40] |
Rezaee AR, Banoei MM, Khalili E, et al. (2012) Beta-Thalassemia in Iran: new insight into the role of genetic admixture and migration. The Scientific World Journal 2012. https://doi.org/10.1100/2012/635183
|
| [41] | Nadkarni A, Gorakshakar AC, Sawant PM, et al. (2019) The phenotypic and molecular diversity of hemoglobinopathies in India: A review of 15 years at a referral center. International journal of laboratoryhematology 41: 218-226. https://doi.org/10.1111/ijlh.12948 |
| [42] |
Shah PS, Shah ND, Ray HSP, et al. (2017) Mutation analysis of β-thalassemia in East-Western Indian population: a recent molecular approach. The application of clinical genetics 10: 27. https://doi.org/10.2147/TACG.S127531
|
| [43] |
Sahoo SS, Biswal S, Dixit M (2014) Distinctive mutation spectrum of the HBB gene in an urban eastern Indian population. Hemoglobin 38: 33-38. https://doi.org/10.3109/03630269.2013.837394
|
| [44] |
Agarwal S, Pradhan M, Gupta UR, et al. (2000) Geographic and ethnic distribution of β-thalassemia mutations in Uttar Pradesh, India. Hemoglobin 24: 89-97. https://doi.org/10.3109/03630260009003427
|
| [45] |
Garewal G, Das R (2003) Spectrum of β-thalassemia mutations in Punjabis. International Journal of Human Genetics 3: 217-219. https://doi.org/10.1080/09723757.2003.11885855
|
| [46] |
Garewal G, Fearon CW, Warren TC, et al. (1994) The molecular basis of β thalassaemia in Punjabi and Maharashtran Indians includes a multilocus aetiology involving triplicated α-globin loci. British journal of haematology 86: 372-376. https://doi.org/10.1111/j.1365-2141.1994.tb04742.x
|
| [47] |
Satpute SB, Bankar MP, Momin AA (2012) The prevalence of β-thalassemia mutations in south western Maharashtra. Indian Journal of Clinical Biochemistry 27: 389-393. https://doi.org/10.1007/s12291-012-0230-y
|
| [48] | Ansari MI, Patel NG (2015) Characterization of β-thalassemia mutations from northMaharashtra region. J Pharm Biol Sci 10: 13-16. |
| [49] |
Bhattacharyya DM, Mukhopadhyay A, Basak J (2014) Descriptive profile of β-756 thalassemia mutations in West Bengal population: a hospital-based study. International journal of hematology 99: 345-353. https://doi.org/10.1007/s12185-014-1511-4
|
| [50] | Grow K, Vashist M, Abrol P, et al. (2014) Beta thalassemia in India:current status and the challenges ahead. Int J Pharm Pharm Sci 6: 28-33. |
| [51] |
Shaji RV, Edison ES, Poonkuzhali B, et al. (2003) Rapid detection of β-globin gene mutations and polymorphisms by temporal temperature gradient gel electrophoresis. Clinical chemistry 49: 777-781. https://doi.org/10.1373/49.5.777
|
| [52] | Borah MS, Bhattacharya PK, Pathak MS, et al. (2016) A hospital based study of Hb variant and beta thalassaemia mutational pattern characterization among the people of Northeast region of India. Annals of Pathology and Laboratory Medicine 3: 134-140. |
| [53] | Boonyawat B, Monsereenusorn C, Traivaree C (2014) Molecular analysis of beta-globin gene mutations among Thai beta-thalassemia children: results from a single center study. The application of clinical genetics 7: 253. https://doi.org/10.2147/TACG.S73058 |
| [54] |
Italia K, Sawant P, Surve R, et al. (2012) Variable haematological and clinical presentation of β-thalassaemia carriers and homozygotes with the P oly A (T→ C) mutation in the Indian population. European journal of haematology 89: 160-164. https://doi.org/10.1111/j.1600-0609.2012.01810.x
|
| [55] |
Kulkarni GD, Kulkarni SS, Kadakol GS, et al. (2012) Molecular basis of β-thalassemia in Karnataka, India. Genetic testing and molecular biomarkers 16: 138-141. https://doi.org/10.1089/gtmb.2011.0035
|
| [56] |
Gorakshakar AC, Pawar AR, Nadkarni AH, et al. (1999) Potential of denaturing gradient gel electrophoresis for scanning of β-thalassemia mutations in India. American journal of hematology 61: 120-125. https://doi.org/10.1002/(SICI)1096-8652(199906)61:2<120::AID-AJH8>3.0.CO;2-T
|
| [57] |
Colah R, Nadkarni A, Gorakshakar A, et al. (2004) Impact of β globin gene mutations on the clinical phenotype of β thalassemia in India. Blood Cells, Molecules, and Diseases 33: 153-157. https://doi.org/10.1016/j.bcmd.2004.05.002
|
| [58] |
Vaz FEE, Thakur CB, Banerjee MK, et al. (2000) Distribution of β-thalassemia mutations in the Indian population referred to a diagnostic center. Hemoglobin 24: 181-194. https://doi.org/10.3109/03630260008997526
|
| [59] |
Banu B, Khan WA, Selimuzzaman M, et al. (2018) Mutation Pattern in Beta Thalassaemia Trait Population: A Basis for Prenatal Diagnosis. Bangladesh Medical Research Council Bulletin 44: 65-70. https://doi.org/10.3329/bmrcb.v44i2.38688
|
| [60] | Thakur C, Vaz F, Banerjee M, et al. (2000) Prenatal diagnosis of β-thalassaemia and other haemoglobinopathies in India. Prenatal Diagnosis: Published in Affiliation With the International Society for Prenatal Diagnosis 20: 194-201. https://doi.org/10.1002/(SICI)1097-0223(200003)20:3<194::AID-PD778>3.0.CO;2-3 |
| [61] |
Abuzenadah AM, Hussein IMR, Damanhouri GA, et al. (2011) Molecular basis of β-thalassemia in the western province of SaudiArabia:identification of rare β-thalassemia mutations. Hemoglobin 35: 346-357. https://doi.org/10.3109/03630269.2011.588508
|
| [62] |
Broquere C, Brudey K, Harteveld CL, et al. (2010) Phenotypic Expression and Origin of the Rare β-Thalassemia Splice Site Mutation HBB: c. 315+ 1G> T. Hemoglobin 34: 322-326. https://doi.org/10.3109/03630269.2010.484956
|
| [63] | IthaGenes (ithanet.eu). Available from: http://www.ithanet.eu/db/ithagenes?ithaID=202 |
| [64] |
Boehm CD, Dowling CE, Waber PG, et al. (1986) Use of oligonucleotide hybridization in the characterization of a beta zero-thalassemia gene (beta 37 TGG TGA) in a Saudi Arabian family. Blood 67: 1185-1188. https://doi.org/10.1182/blood.V67.4.1185.1185
|
| [65] |
Vrettou C, Traeger-Synodinos J, Tzetis M, et al. (2003) Rapid screening of multiple β-globin gene mutations by real-time PCR on the Light Cycler: application to carrier screening and prenatal diagnosis of thalassemia syndromes. Clinical chemistry 49: 769-776. https://doi.org/10.1373/49.5.769
|
| [66] |
De Sanctis V, Kattamis C, Canatan D, et al. (2017) β-Thalassemia distribution in the old world: an ancient disease seen from a historical standpoint. Mediterranean journal of hematology and infectious diseases 9. https://doi.org/10.4084/MJHID.2017.018
|
| [67] |
Christopoulos G, Ezzat GM, Kleanthous M (2012) Use of denaturing gradient gel electrophoresis in screening unknown β-thalassemia mutations in Egyptian patients. Egyptian Journal of Medical Human Genetics 13: 343-349. https://doi.org/10.1016/j.ejmhg.2012.06.008
|
| [68] |
Fernandes AC, Azevedo Shimmoto MM, Furuzawa GK, et al. (2011) Molecular analysis of β-thalassemia patients: First identification of mutations HBB: c. 816 93-2A> G and HBB: c. 114G> A in Brazil. Hemoglobin 35: 358-366. https://doi.org/10.3109/03630269.2011.588354
|
| [69] |
Georgiou I, Makis A, Chaidos A, et al. (2003) Distribution and frequency of β-thalassemia mutations in northwestern and central Greece. European journal of haematology 70: 75-78. https://doi.org/10.1034/j.1600-0609.2003.00017.x
|
| [70] |
Talmaci R, Traeger-Synodinos J, Kanavakis E, et al. (2004) Scanning of β-globin gene for identification of β-thalassemia mutation in Romanian population. Journal of Cellular and Molecular Medicine 8: 232-240. https://doi.org/10.1111/j.1582-4934.2004.tb00278.x
|
| [71] | Kamilia B, Mouloud Y, Moez G, et al. (2017) The predominance of codon 39 (c> t) mutation of HBB gene in a portion of the Algerian population (Northeast Algeria). Journal of Biological Research-Bollettinodella Società Italianadi Biologia Sperimentale 90. https://doi.org/10.4081/jbr.2017.6407 |
| [72] | Gomes WR, Santos RA, Cominal JG, et al. (2017) Frequencies of CD39, IVS1-1, IVS1-6 and IVS1-110 mutations in beta-thalassemia carriers and their influence on hematimetric indices. Journal Brasileiro de Patologia e Medicina Laboratorial 53: 362-367. https://doi.org/10.5935/1676-2444.20170058 |
| [73] |
Warsy AS, ElHazmi MA, Al Momin AK, et al. (2013) Extensive polymorphisms in saudi beta thalassaemia patients. Biosciences, Biotechnology Research Asia 10: 127-132.
|
| [74] |
Murad H, Moasses F, Dabboul A, et al. (2018) Geographical distribution of β-globin gene mutations in Syria. Hematology 23: 697-704. https://doi.org/10.1080/10245332.2018.1461291
|
| [75] |
Jaripour ME, Hayatigolkhatmi K, Iranmanesh V, et al. (2018) Prevalence of β-thalassemia mutations among Northeastern Iranian population and their impacts on hematological indices and application of prenatal diagnosis, a seven-years study. Mediterranean journal of hematology and infectious diseases 10: 1. https://doi.org/10.4084/MJHID.2018.042
|
| [76] | Derakhshandeh-Peykar P, Hourfar H, Heidari M, et al. (2008) The spectrum of β-thalassemia mutations in Isfahan Province of Iran. Iranian Journal of Public Health 2008: 106-111. |
| [77] |
Hyde RD, Hall MD, Wiltshire BG, et al. (1972) Haemoglobin Southampton, β106(G8) Leu→Pro: an unstable variant producing severe haemolysis. Lancet 2: 1170-1172. https://doi.org/10.1016/S0140-6736(72)92594-9
|
| [78] |
EandiEberle S, Noguera NI, Sciuccati G, et al. (2006) Hb Southampton [β106 (G8) Leu→ Pro, CTG→ CCG] in an Argentinean boy. Hemoglobin 2006: 401-403. https://doi.org/10.1080/03630260600755930
|
| [79] |
Pereira JADL, López P, Costa FF, et al. (2013) Hb Southampton [B106 (G8) Leu→ PRO, CTG→ CCG] in a Uruguayan woman. Rev Bras Hematol Hemoter 35: 146-147. https://doi.org/10.5581/1516-8484.20130037
|
| [80] | DeCastro CM, Fleenor E, Lee E, et al. A Novel β-Globin Mutation, β Durham-NC [β l 14 Leu” Pro], Produces a Dominant Thalassemia-Like Phenotype (1994)1994: 1109-1116. https://doi.org/10.1182/blood.V83.4.1109.1109 |
| [81] |
Açürük M, Molchanova TP, Postnikov YV, et al. (1994) β-thalassemia alleles and unstable hemoglobin types among russian pediatric patients. American journal of hematology 46: 329-332. https://doi.org/10.1002/ajh.2830460413
|
| [82] |
Henderson SJ, Timbs AT, McCarthy J, et al. (2016) Ten years of routine α- and β-globin gene sequencing in UK hemoglobinopathy referrals reveals 60 novel mutations. Hemoglobin 40: 75-84. https://doi.org/10.3109/03630269.2015.1113990
|
| [83] |
Nagar R, Sinha S, Raman R (2015) Haemoglobinopathies in eastern Indian states: ademographic evaluation. Journal of community genetics 6: 1-8. https://doi.org/10.1007/s12687-014-0195-z
|
| [84] |
Jankovic L, Efremov GD, Petkov G, et al. (1990) Two novel polyadenylation mutations leading to β+-thalassaemia. British journal of haematology 75: 122-126. https://doi.org/10.1111/j.1365-2141.1990.00122.x
|
| [85] |
Al-Amodi AM, Ghanem NZ, Aldakeel SA, et al. (2018) Hemoglobin A2 (HbA2) has a measure of unreliability in diagnosing β-thalassemiatrait (β-TT). Current medical research and opinion 34: 945-951. https://doi.org/10.1080/03007995.2018.1435520
|
| [86] |
Das S, Mashon RS (2015) Coinheritance of Hb D-Punjab and β-thalassemia: Diagnosis and implications in prenatal diagnosis. Hemoglobin 39: 138-140. https://doi.org/10.3109/03630269.2015.1004335
|
Figures(2) / Tables(11)
Bhuvana Selvaraj, Ganesan Subramanian, Senthil Kumar Ramanathan, Sangeetha Soundararajan, Shettu Narayanasamy. Studies on molecular spectrum of beta thalassemia among residents of Chennai[J]. AIMS Molecular Science, 2022, 9(3): 107-135. doi: 10.3934/molsci.2022007
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