α-Thalassemia (α-thal) is considered as the most common inherited hemoglobin disorder worldwide. The present study describes the first observation of a combination of rare α-chain variants, and β-globin gene cluster deletion. A 21-year-old woman with thalassemia trait, marked microcytosis, mild anemia, and normal range of Hb F was referred to Amirkola genetic center in the North of Iran for routine molecular test of thalassemia in the context of carrier detection and prevention of thalassemia major birth. Nucleotide sequencing revealed a novel compound heterozygosity status for two non-deletional mutations on HBA2, Hb O Indonesia (α116(GH4)Glu → Lys), and Hb Matsue–Oki (α75 (EF4) Asp → Asn), together with heterozygosity for the sicilian (δβ)0-thal mutation. This finding highlights the necessity of deep molecular investigation of thalassemia in regions where thalassemia is abundant, and present highly heterogeneous population.
α-Thalassemia (α-thal) HBA2Mutation HbF Iran
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Conflict of interest
Authors declare no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institution.
Higgs D, Vickers M, Wilkie A, Pretorius I, Jarman A, Weatherall D. A review of the molecular genetics of the human a-globin gene cluster. Blood. 1989;73:1081–104.PubMedGoogle Scholar
Wajcman H, Traeger-Synodinos J, Papassotiriou I, Giordano PC, Harteveld CL, Baudin-Creuza V, et al. Unstable and thalassemic α chain hemoglobin variants: a cause of Hb H disease and thalassemia intermedia. Hemoglobin. 2008;32:327–49.CrossRefPubMedGoogle Scholar
Eftekhari H, Tamaddoni A, Mahmoudi Nesheli H, Vakili M, Sedaghat S, Banihashemi A, et al. A comprehensive molecular investigation of α-thalassemia in an iranian cohort from different provinces of North Iran. Hemoglobin. 2017;41(1):32–7.CrossRefPubMedGoogle Scholar
Molchanova TP, Pobedimskaya DD, Huisman TH. The differences in quantities of alpha 2- and alpha 1-globin gene variants in heterozygotes. Br J Haematol. 1994;88:300–6.CrossRefPubMedGoogle Scholar
Henderson SJ, Timbs AT, McCarthy J, Gallienne AE, Proven M, Rugless MJ, et al. Ten years of routine alpha- and beta-globin gene sequencing in UK hemoglobinopathy referrals reveals 60 novel mutations. Hemoglobin. 2016;40:75–84.CrossRefPubMedGoogle Scholar
Daud D, Harahap A, Setianingsih I, Nainggolan I, Tranggana S, Pakasi R, et al. The hemoglobin O mutation in Indonesia: distribution and phenotypic expression. J Hum Genet. 2001;46:499–505.CrossRefPubMedGoogle Scholar
Upadhye DS, Jain D, Nair SB, Nadkarni AH, Ghosh K, Colah RB. First case of Hb Fontainebleau with sickle haemoglobin and other non-deletional α gene variants identified in neonates during newborn screening for sickle cell disorders. J Clin Pathol. 2012;65:654–9.CrossRefPubMedGoogle Scholar
Yi-Tao Z, Headlee M, Henson J, Lam H, Wilson J, Huisman T. Identification of hemoglobin G-Philadelphia (α68 Asn → Lys) and homoglonin Matsue–Oki (α75 Asp → Asn) in a black infant. Biochim Biophys Acta Prot Struct Mol Enzymol. 1982;707:206–12.CrossRefGoogle Scholar
van Zwieten R, Veldthuis M, Delzenne B, Berghuis J, Groen J, Ait Ichou F, et al. Hemoglobin analyses in The Netherlands reveal more than 80 different variants including six novel ones. Hemoglobin. 2014;38:1–7.CrossRefPubMedGoogle Scholar