Abstract
Co-inheritance of triplicated α-genes can alter the clinical and hematological phenotypes of β-thalassemias. We evaluated the phenotypic diversity and transfusion requirements in β-thalassemia heterozygotes, homozygotes, and normal individuals with associated α-gene triplication. Clinical and hematological evaluation was done and the β-thalassemia mutations characterized by a covalent reverse dot blot hybridization/amplification refractory mutation system. Alpha-globin gene triplication was assessed by multiplex PCR. During the last 2.5 years, 181 β-thalassemia patients and β-thalassemia carriers with an unusual clinical presentation were referred to us for screening for the presence of associated α-globin gene triplication. Twenty-nine of them had associated α-gene triplication (3 β-thalassemia homozygotes or compound heterozygotes and 26 β-thalassemia heterozygotes). One β-thalassemia compound heterozygote [IVS 1–5 (G → C) + CD 41/42 (−CTTT)] was anemic at birth and required blood transfusions unusually early by 6 weeks of age. The second patient (4.5 years) was also clinically severe and became transfusion dependent in spite of having one mild β-thalassemia mutation [Capsite +1 (A → C)]. The third case (3.5 years) who was homozygous for a mild β-gene mutation [−88 (C → T)] with α gene triplication was untransfused. The 26 β-thalassemia heterozygotes with associated triplicated α-genes presented variably, with a β-thalassemia intermedia-like presentation. While screening the family members of all these cases, we found another 10 β-thalassemia heterozygotes and 9 normal individuals with α-globin gene triplication; however, all of them were asymptomatic. Beta-thalassemia carriers, homozygotes, and compound heterozygotes with an unusual presentation should be screened for the possible presence of associated α-globin gene triplication which could influence the clinical and hematological presentation.
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Abbreviations
- HPLC:
-
High-performance liquid chromatography
- CRDB:
-
Covalent reverse dot blot hybridization
- ARMS:
-
Amplification refractory mutation system
- TI:
-
Thalassemia intermedia
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We are thankful to all the clinicians for referring the patients.
Authorship contributions
PM, DU, and MG carried out the molecular analysis for alpha-gene triplication, and PM wrote the first draft of the manuscript. PS helped with the molecular analysis for β-thalassemia, AN supervised the laboratory work, and CS clinically evaluated the patients. RC designed the study, helped with the analysis of the data, and finalized the manuscript. KG provided inputs for the manuscript. All the authors have read and approved the manuscript.
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Mehta, P.R., Upadhye, D.S., Sawant, P.M. et al. Diverse phenotypes and transfusion requirements due to interaction of β-thalassemias with triplicated α-globin genes. Ann Hematol 94, 1953–1958 (2015). https://doi.org/10.1007/s00277-015-2479-8
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DOI: https://doi.org/10.1007/s00277-015-2479-8