Vol 14 (2023): Continuous Publishing
Research paper
Published online: 2023-06-15
Study of type and frequency of Alfa-thalassemia mutations in a cohort of 3,823 patients from Isfahan Province, Iran
1, 23, 4, 23, 1, 3
, 2, 13, 2
, 2, 13, 2
Hematol Clin Pract 2023;14:24-29.
Abstract
Introduction: Alpha-thalassemia (α-thalassemia) is caused by a range of mutations in the α-globin gene resulting in the complete reduction or absence of α-globin chain production. Material and methods: This study assessed the presence of α-thalassemia in 3,823 patients referred to Al-Zahra Hospital, Isfahan, Iran during a 10-year period (from 2012 to 2022). These patients experienced anaemia for more than ten years but had not the full indication for β-thalassemia or iron deficiency. Results: Based on the present assessment, 3,483 cases out of 3,823 suspicious cases had an α-Thalassemia-involved mutation (91.1%). According to the results, the most common detected mutation in the α-thalassemia carriers of Isfahan province was –α3.7 with a frequency of 81.58% (3,119 individuals), followed by α5nt (–TGAGG) (3.71% in total or 39.01% between 364 patients), polyadenylation signal mutations (polyA2) (14.28% between 364 patients), αcodon 19 (GCG4GC–, a2) (11.53%), –α3.7/–α3.7 (11.53%), –α20.5 (7.69%), Hb Constant Spring [Hb CS, a142, Stop →Gln; HBA2: c.427T4C] (5.7%), α4.2 (5.49) and – –MED (4.67%). Conclusion: The results of this investigation may be valuable for designing a program for carrier screening, premarital genetic counselling, and prenatal diagnosis in the Isfahan province.
Keywords: thalassemiaalpha-thalassemiascreeningprenatal diagnosis (PND)genetic counseling
References
- 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; 30(6): 493–508.
- Weatherall DJ, Clegg JB. Inherited haemoglobin disorders: an increasing global health problem. Bull World Health Organ. 2001; 79(8): 704–712.
- Weatherall DJ. Phenotype-genotype relationships in monogenic disease: lessons from the thalassaemias. Nat Rev Genet. 2001; 2(4): 245–255.
- Harteveld CL, Higgs D. α-thalassaemia. Orphanet Journal of Rare Diseases. 2010; 5(1).
- Piel FB, Weatherall DJ. The α-thalassemias. N Engl J Med. 2014; 371(20): 1908–1916.
- Zhang J, Zhu BS, He J, et al. The spectrum of α- and β-thalassemia mutations in Yunnan Province of Southwestern China. Hemoglobin. 2012; 36(5): 464–473.
- Karamzade A, Mirzapour H, Hoseinzade M, et al. α-globin gene mutations in Isfahan Province, Iran. Hemoglobin. 2014; 38(3): 161–164.
- Xu XM, Zhou YQ, Luo GX, et al. The prevalence and spectrum of alpha and beta thalassaemia in Guangdong Province: implications for the future health burden and population screening. J Clin Pathol. 2004; 57(5): 517–522.
- Samavat A, Modell B. Iranian national thalassaemia screening programme. BMJ. 2004; 329(7475): 1134–1137.
- Hadavi V, Taromchi AH, Malekpour M, et al. Elucidating the spectrum of alpha-thalassemia mutations in Iran. Haematologica. 2007; 92(7): 992–993.
- Neyshabouri M, Abbasi-Moheb L, Kahrizi K, et al. Alpha-thalassemia: deletion analysis in Iran. Arch Irn Med. 2001; 4(4): 160–164.
- Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988; 16(3): 1215.
- Chong SS, Boehm CD, Higgs DR, et al. Single-tube multiplex-PCR screen for common deletional determinants of α-thalassemia. Blood. 2000; 95(1): 360–362.
- Khosravi A, Jalali-Far M, Saki N, et al. Evaluation of α-globin gene mutations among different ethnic groups in Khuzestan Province, Southwest Iran. Hemoglobin. 2016; 40(2): 113–117.
- Hashemi-Soteh SM, Karami H, Mousavi SS, et al. Alpha-globin gene mutation spectrum in patients with microcytic hypochromic anemia from Mazandaran Province, Iran. J Clin Lab Anal. 2020; 34(1): e23018.
- Saleh-Gohari N, Khosravi-Mashizi A. Spectrum of α-globin gene mutations in the Kerman Province of Iran. Hemoglobin. 2010; 34(5): 451–460.
- Moradi K, Aznab M, Biglari M, et al. Molecular genetic analysis of α-thalassemia in Hamadan Province, West Iran. Hemoglobin. 2020; 44(5): 319–324.
- Moradi K, Aznab M, Tahmasebi S, et al. The spectrum of α-thalassemia mutations in the Lak population of Iran. Hemoglobin. 2019; 43(2): 107–111.
- Harteveld CL, Yavarian M, Zorai A, et al. Molecular spectrum of alpha-thalassemia in the Iranian population of Hormozgan: three novel point mutation defects. Am J Hematol. 2003; 74(2): 99–103.
- Eftekhari H, Tamaddoni A, Mahmoudi Nesheli H, et al. A comprehensive molecular investigation of α-thalassemia in an Iranian cohort from different provinces of North Iran. Hemoglobin. 2017; 41(1): 32–37.
- Dehbozorgian J, Moghadam M, Daryanoush S, et al. Distribution of alpha-thalassemia mutations in Iranian population. Hematology. 2015; 20(6): 359–362.
- Pouranfard J, Vafaei F, Rezaeian M, et al. Thalassemia gene mutations in Kohgiluyeh and Boyer-Ahmad province. IJBC. 2020; 12(1): 18–23.
- Moradi K, Aznab M, Biglari M, et al. Molecular genetic analysis of α-thalassemia in Hamadan Province, West Iran. Hemoglobin. 2020; 44(5): 147–152.
- Alibakhshi R, Moradi K, Aznab M, et al. The spectrum of α-thalassemia mutations in Kurdistan Province, West Iran. Hemoglobin. 2020; 44(3): 156–161.
- Derakhshan SM, Khaniani MS, Afkhami F, et al. Molecular study of deletional and nondeletional mutations on the α-globin locus in the Azeri population of Northwestern Iran. Hemoglobin. 2016; 40(5): 319–322.
- Miri-Moghaddam E, Nikravesh A, Gasemzadeh N, et al. Spectrum of alpha-globin gene mutations among premarital Baluch couples in southeastern Iran. Int J Hematol Oncol Stem Cell Res. 2015; 9(3): 138–142.
- Zarbakhsh B, Farshadi E, Ariani Kashani A, et al. Molecular study of alpha-thalassemia mutations in Iranian potential carriers. Sci J Iran Blood Transfus Org. 2010; 7(2): 70–77.
- Valaei A, Karimipoor M, Kordafshari A, et al. Molecular basis of α-thalassemia in Iran. Iran Biomed J. 2018; 22(1): 6–14.
- Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ. 2008; 86(6): 480–487.
- Hossein F, Mohsen R, Mohsen M, et al. α-thalassemia mutations in two provinces of Southern Iran: Fars & Kohkeloye and Bouyer Ahmad. Hemoglobin. 2012; 36(2): 139–143.
- Hadavi V, Jafroodi M, Hafezi-Nejad N, et al. Alpha-thalassemia mutations in Gilan Province, North Iran. Hemoglobin. 2009; 33(3): 235–241.
- Sarookhani MR, Asiabanha M. Spectrum of α-thalassemia mutations in Qazvin Province, Iran. African Journal of Biotechnology. 2011; 10(77): 17690–17694.
- Abolghasemi H, Amid A, Zeinali S, et al. Thalassemia in Iran: epidemiology, prevention, and management. J Pediatr Hematol Oncol. 2007; 29(4): 233–238.
- Zareifar S, Jabbari A, Cohan N, et al. Efficacy of combined desferrioxamine and deferiprone versus single desferrioxamine therapy in patients with major thalassemia. Arch Iran Med. 2009; 12(5): 488–491.
- Tamaddoni A, Hadavi V, Nejad NH, et al. Alpha-thalassemia mutation analyses in Mazandaran province, North Iran. Hemoglobin. 2009; 33(2): 115–123.
- El-Kalla S, Baysal E. Alpha-thalassemia in the United Arab Emirates. Acta Haematol. 1998; 100(1): 49–53.
- Nashtahosseini Z, Nazemi A, Keihanian S, et al. Frequency of seven common deletion alfa-globins mutation carriers in suspect referred In West Mazandaran, Iran. Electronic J Biol. 2016; 12(1): 18–21.
- Rahim F. Microcytic hypochromic anemia patients with thalassemia : Genotyping approach. Indian Journal of Medical Sciences. 2009; 63(3): 101.
- Hardison RC, Chui DHK, Giardine B, et al. HbVar: a relational database of human hemoglobin variants and thalassemia mutations at the globin gene server. Hum Mutat. 2002; 19(3): 225–233.
