Complete molecular spectrum of β-globin gene mutations via direct sequencing identifies seven novel variants in β-thalassemia major
Torin Abdulaziz Sadoon, Hemin Esmael OthmanTorin Abdulaziz Sadoon, Hemin Esmael Othman
Abstract
Background
A common monogenic condition, β-thalassemia, is caused by a variety of mutations in the β-globin (HBB) gene. It is essential to accurately characterize these mutations for genetic counselling, diagnosis, and treatment.
Introduction
β-thalassemia is a widespread anemia of a monogenic hereditary disorder with an autosomal recessive pattern of inheritance that occurs due to mutations in the beta-globin gene (HBB) [1]. The degree of β-globin chain imbalance is determined by the nature of the mutation of the β-globin gene. β0 refers to the complete absence of β-globin from the affected allele. β+ refers to alleles with some residual production of β-globin (around 10%). In β++, the reduction in β-globin production is very mild.
Materials and method
Design and setting of the study
This cross-sectional study was carried out at the Thalassemia Disease Centre at Jeen Hospital in Duhok City, Kurdistan Region, Iraq.
Results
In the current study, a complete spectrum of β-globin gene (HBB) mutations was detected and reported. Of the 60 enrolled patients, 40 yielded high-quality, analyzable DNA sequence chromatograms. Out of them, 26 distinct mutations were identified, comprising 16 intronic and 10 exonic variants.
Discussion
The current study broadens the genetic epidemiology of β-thalassemia in Iraq by identifying 26 different HBB variations in a patient cohort under study, including seven previously unknown alterations. The global pattern of a relatively small core of highly prevalent mutations accompanied by a long “tail” of population- or family-specific changes is reflected in this breadth of allelic diversity.
Acknowledgments
We express our gratitude to the Thalassaemia Disease Centre and the Duhok Central Laboratory of the Directorate General of Health in Duhok, Kurdistan Region-Iraq, for their invaluable assistance and provision of all facilities.
Citation: Sadoon TA, Othman HE (2025) Complete molecular spectrum of β-globin gene mutations via direct sequencing identifies seven novel variants in β-thalassemia major. PLoS One 20(11): e0336610. https://doi.org/10.1371/journal.pone.0336610
Editor: Nejat Mahdieh, Shaheed Rajaei Cardiovascular Medical and Research Center: Rajaie Cardiovascular Medical and Research Center, IRAN, ISLAMIC REPUBLIC OF
Received: July 1, 2025; Accepted: October 28, 2025; Published: November 7, 2025
Copyright: © 2025 Sadoon, Othman. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the manuscript and its Supporting information files.
Funding: The author(s) received no specific funding for this work.
Competing interests: No conflicting interests are disclosed by the authors.
