Hb SKMC and an unprecedented γδβ-thalassemia: first report from Iraq

Background Thalassemias are genetic disorders of globin chain synthesis. In Iraq, β-thalassemia is more prevalent than α-thalassemia. This study identifies two unpredicted globin gene mutations, a rare α-globin gene mutation (Hb SKMC) and a novel γδβ-thalassemia deletion.Methods Over 2 years, the Ge...

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Main Authors: Rawand P. Shamoon, Amir Charkaneh, Elena Di Pierro, Milena Irrera, Cristina Curcio, Ahmed Yassin, Rozhgar A. Khailany
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Hematology
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Online Access:https://www.tandfonline.com/doi/10.1080/16078454.2024.2399356
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author Rawand P. Shamoon
Amir Charkaneh
Elena Di Pierro
Milena Irrera
Cristina Curcio
Ahmed Yassin
Rozhgar A. Khailany
author_facet Rawand P. Shamoon
Amir Charkaneh
Elena Di Pierro
Milena Irrera
Cristina Curcio
Ahmed Yassin
Rozhgar A. Khailany
author_sort Rawand P. Shamoon
collection DOAJ
description Background Thalassemias are genetic disorders of globin chain synthesis. In Iraq, β-thalassemia is more prevalent than α-thalassemia. This study identifies two unpredicted globin gene mutations, a rare α-globin gene mutation (Hb SKMC) and a novel γδβ-thalassemia deletion.Methods Over 2 years, the Genetics unit at PAR hospital in Erbil, northern Iraq processed 137 β-thalassemia and 97 α-thalassemia genetic testing requests. Three symptomatic thalassemia cases with unreported genotypes were identified. Proband-1α and proband-2α had Hb H disease, while proband-1β had severe transfusion-dependent β-thalassemia (TDT). Molecular studies included multiplex PCR, reverse hybridization, multiplex ligation-dependent probe amplification (MLPA), and globin gene sequencing.Results The α-thalassemia probands exhibited moderate microcytic hypochromic anemia with irregular transfusions and splenomegaly. Hb H disease was confirmed by positive Hb H tests and high-performance liquid chromatography (HPLC). Molecular analysis revealed heterozygous –MED deletion in proband-1α and α2Poly-A2 mutation in proband-2α. Sequencing identified the Hb SKMC (HBA1:c.283_300+3dup) mutation in both probands. The β-thalassemia proband showed anemia and regular transfusions. Molecular studies detected the IVS1.110 G>A mutation and a novel γδβ-thalassemia deletion in compound heterozygous form. The maternal sample showed the IVS1.110 G>A mutation, and MLPA confirmed the γδβ-thalassemia deletion in the paternal sample.Conclusion These findings highlight the genetic diversity of thalassemias in the region and emphasize the importance of advanced molecular diagnostics in detecting rare mutations.
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spelling doaj-art-cb6c7b1af1674f8286969f500083ff2d2025-08-20T02:34:31ZengTaylor & Francis GroupHematology1607-84542024-12-0129110.1080/16078454.2024.2399356Hb SKMC and an unprecedented γδβ-thalassemia: first report from IraqRawand P. Shamoon0Amir Charkaneh1Elena Di Pierro2Milena Irrera3Cristina Curcio4Ahmed Yassin5Rozhgar A. Khailany6Department of Pathology, College of Medicine, Hawler Medical University, Erbil, IraqGenetics Unit, Laboratory Division, PAR Private Hospital, Erbil, IraqMedicine and Metabolic Diseases Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyClinical Pathology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyClinical Pathology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyDepartment of Internal Medicine, College of Medicine, Hawler Medical University, Erbil, IraqDepartment of Microbiology and Genetics, College of Medicine, Hawler Medical University, Erbil, IraqBackground Thalassemias are genetic disorders of globin chain synthesis. In Iraq, β-thalassemia is more prevalent than α-thalassemia. This study identifies two unpredicted globin gene mutations, a rare α-globin gene mutation (Hb SKMC) and a novel γδβ-thalassemia deletion.Methods Over 2 years, the Genetics unit at PAR hospital in Erbil, northern Iraq processed 137 β-thalassemia and 97 α-thalassemia genetic testing requests. Three symptomatic thalassemia cases with unreported genotypes were identified. Proband-1α and proband-2α had Hb H disease, while proband-1β had severe transfusion-dependent β-thalassemia (TDT). Molecular studies included multiplex PCR, reverse hybridization, multiplex ligation-dependent probe amplification (MLPA), and globin gene sequencing.Results The α-thalassemia probands exhibited moderate microcytic hypochromic anemia with irregular transfusions and splenomegaly. Hb H disease was confirmed by positive Hb H tests and high-performance liquid chromatography (HPLC). Molecular analysis revealed heterozygous –MED deletion in proband-1α and α2Poly-A2 mutation in proband-2α. Sequencing identified the Hb SKMC (HBA1:c.283_300+3dup) mutation in both probands. The β-thalassemia proband showed anemia and regular transfusions. Molecular studies detected the IVS1.110 G>A mutation and a novel γδβ-thalassemia deletion in compound heterozygous form. The maternal sample showed the IVS1.110 G>A mutation, and MLPA confirmed the γδβ-thalassemia deletion in the paternal sample.Conclusion These findings highlight the genetic diversity of thalassemias in the region and emphasize the importance of advanced molecular diagnostics in detecting rare mutations.https://www.tandfonline.com/doi/10.1080/16078454.2024.2399356Hb SKMCγδβ-thalassemiaϵγδβ-thalassemiaα-thalassemiaβ-thalassemiaIraq
spellingShingle Rawand P. Shamoon
Amir Charkaneh
Elena Di Pierro
Milena Irrera
Cristina Curcio
Ahmed Yassin
Rozhgar A. Khailany
Hb SKMC and an unprecedented γδβ-thalassemia: first report from Iraq
Hematology
Hb SKMC
γδβ-thalassemia
ϵγδβ-thalassemia
α-thalassemia
β-thalassemia
Iraq
title Hb SKMC and an unprecedented γδβ-thalassemia: first report from Iraq
title_full Hb SKMC and an unprecedented γδβ-thalassemia: first report from Iraq
title_fullStr Hb SKMC and an unprecedented γδβ-thalassemia: first report from Iraq
title_full_unstemmed Hb SKMC and an unprecedented γδβ-thalassemia: first report from Iraq
title_short Hb SKMC and an unprecedented γδβ-thalassemia: first report from Iraq
title_sort hb skmc and an unprecedented γδβ thalassemia first report from iraq
topic Hb SKMC
γδβ-thalassemia
ϵγδβ-thalassemia
α-thalassemia
β-thalassemia
Iraq
url https://www.tandfonline.com/doi/10.1080/16078454.2024.2399356
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