PREVALENCE OF ß-THALASSEMIA MUTATIONS AMONG NORTHEASTERN IRANIAN POPULATION AND THEIR IMPACTS ON HEMATOLOGICAL INDICES AND APPLICATION OF PRENATAL DIAGNOSIS, A SEVEN-YEARS STUDY
Main Article Content
Keywords
ß-thalassemia, mutation prevalence, complete blood count, prenatal diagnosis, Khorasan
Abstract
Background and objective: ß-thalassemia results from a diverse range of mutations inside the hemoglobin subunit ? (HBB) gene. In a study of ?-thalassemia carriers and some of their at-risk fetuses in the Khorasan province of Iran we aimed to recognize the most common mutations in the region and to find a possible link between these mutations and some of the relevant hematological indices.
Methods: Amplification-refractory mutation system-PCR (ARMS-PCR) was used to detect the typical HBB mutations among 1593 individuals, suspected of having a mutated HBB allele from March/2011 to January/2018. Sanger sequencing of HBB had been performed, where ARMS-PCR was uninformative. In some cases, reverse dot blot was utilized. Analysis of variance was used to compare parametric variables.
Results: Among 1273 ß-thalassemia carriers, the prevalence of the mutations were reported as follows: IVS-I-5 (42.03%), IVS-II-1 (11.23%), Codons 8/9 (4.79%), Codon 44 (4.56%), codon 15 (3.53%), Los Angeles (2.91%), Codon 5 (2.75%), IVS-I-110 (2.51%), -88 (2.20%) and other mutations were less than 2% of all of the reported mutations. 644 conceptions were subjected to prenatal diagnosis, using chorionic villus sampling. 118 cases were reported as normal. 352 cases were detected as carriers. 174 cases were diagnosed as affected. There was a significant difference in mean corpuscular volume and hemoglobin A2 levels between the 9 most commonly reported mutation types (p<0.001).
Conclusion: This study makes a reliable guide for ß-thalassemia diagnosis in the region. The possibility of a correlation between HBB mutations and hematological indices opens a gate of future investigations.
Downloads
Abstract 1973
PDF Downloads 619
HTML Downloads 272
Supplementary table 1 Downloads 0
Some of the mutation detection samples Downloads 0
References
[2] Campbell JS. Alpha and beta thalassemia. Am Fam Physician. 2009 Aug 15;80(4). PMid: 19678601
[3] Irani AD, Cheraghi Z, Bitaraf S, Cheraghi P, Safiri S. Prevalence of alpha and beta-thalassemia mutations among carriers of thalassemia in Shadegan city, southwest of Iran. Zahedan J Res Med Sci. 2015;17(8). http://dx.doi.org/10.17795/zjrms1032
[4] Rahimi Z, Raygani AV, Merat A, Haghshenass M, Gerard N, Nagel RL, Krishnamoorthy R. Thalassemic mutations in southern Iran. Iran J Med Sci. 2015 Aug 31;31(2).
[5] Rezaee AR, Banoei MM, Khalili E, Houshmand M. Beta-Thalassemia in Iran: new insight into the role of genetic admixture and migration. ScientificWorldJournal. 2012;2012. https://doi.org/10.1100/2012/635183 PMid: 23319887
[6] Mahdieh N, Rabbani B. Beta thalassemia in 31,734 cases with HBB gene mutations: pathogenic and structural analysis of the common mutations; Iran as the crossroads of the Middle East. Blood Rev. 2016 Nov 1;30(6):493-508. https://doi.org/10.1016/j.blre.2016.07.001 PMid: 27453201
[7] Sarookhani MR, Ahmadi MH, Amirizadeh N. Molecular Spectrum of Beta-Globin Mutations in Transfusion-Dependent Patients with Thalassemia in Qazvin Province, Iran. Iran J Med Sci. 2015 May 12;34(1):17-22.
[8] Sarookhani MR, Ahmadi MH. Rare and unexpected beta thalassemic mutations in Qazvin province of Iran. Afr J Biotechnol. 2010;9(1).
[9] Derakhshandeh-Peykar P, Hourfar H, Heidari M, Kheirollahi M, Miryounesi M. The spectrum of ?-thalassemia mutations in Isfahan Province of Iran. Iran J Public Health. 2008;37(2):106-11.
[10] Derakhshandeh-Peykar P, Akhavan-Niaki H, Tamaddoni A, Ghawidel-Parsa S, Holakouie Naieni K, Rahmani M, Babrzadeh F, Dilmaghani-Zadeh M, Daneshvar Farhud D. Distribution of ?-thalassemia mutations in the northern provinces of Iran. Hemoglobin. 2007 Jan 1;31(3):351-6. https://doi.org/10.1080/03630260701462030
[11] Rahimi F, Keikhani B, Aberumand M. Prenatal diagnosis (PND) of ?-thalassemia in the Khuzestan province, Iran. J Clin Diagn Res. 2007 Jan 1;1(6):454-9.
[12] Najmabadi H, Ghamari A, Sahebjam F, Kariminejad R, Hadavi V, Khatibi T, Samavat A, Mehdipour E, Modell B, Kariminejad MH. Fourteen-year experience of prenatal diagnosis of thalassemia in Iran. Public Health Genomics. 2006;9(2):93-7. https://doi.org/10.1159/000091486 PMid: 16612059
[13] Abolghasemi H, Amid A, Zeinali S, Radfar MH, Eshghi P, Rahiminejad MS, Ehsani MA, Najmabadi H, Akbari MT, Afrasiabi A, Akhavan-Niaki H. Thalassemia in Iran: epidemiology, prevention, and management. J Pediatr Hematol Oncol. 2007 Apr 1;29(4):233-8. https://doi.org/10.1097/MPH.0b013e3180437e02 PMid: 17414565
[14] Langlois S, Ford JC, Chitayat D, Désilets VA, Farrell SA, Geraghty M, Nelson T, Nikkel SM, Shugar A, Skidmore D, Allen VM. Carrier screening for thalassemia and hemoglobinopathies in Canada. J Obstet Gynaecol Can. 2008 Oct 1;30(10):950-9. https://doi.org/10.1016/S1701-2163(16)32975-9 PMid: 19038079
[15] Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988 Feb 11;16(3):1215. PMid: 3344216
[16] Old JM, Varawalla NY, Weatherall DJ. Rapid detection and prenatal diagnosis of ?-thalassaemia: studies in Indian and Cypriot populations in the UK. Lancet. 1990 Oct 6;336(8719):834-7. PMid: 1976877
[17] Giardine B, van Baal S, Kaimakis P, Riemer C, Miller W, Samara M, Kollia P, Anagnou NP, Chui DH, Wajcman H, Hardison RC. HbVar database of human hemoglobin variants and thalassemia mutations: 2007 update. Hum mutat. 2007 Feb 1;28(2):206-. https://doi.org/10.1002/humu.9479 PMid: 17221864