Genotypic-Phenotypic Correlations in Non-HbE β-Thalassemia Intermedia: A Geographic Systematic Review.
4 affiliations
- 1Department of Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka.
- 2NK Ceylon Institute of Medical Research, Negombo, Sri Lanka.
- 3Department of Medicine, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka.
- 4University Medical Unit, Colombo North Teaching Hospital, Ragama, Sri Lanka.
Abstract
Background
β-thalassemia intermedia (β-TI), now more commonly classified within the spectrum of non-transfusion-dependent thalassemia (NTDT), is a clinically heterogeneous disorder in which disease severity is determined not only by β-globin mutations but also by co-inherited genetic modifiers that vary across populations. These include α-globin gene alterations, fetal haemoglobin (HbF)-inducing polymorphisms, and other regulatory loci that influence globin chain balance.Methods
A systematic review was conducted in accordance with PRISMA 2020 guidelines. PubMed was searched from inception to May 2026, supplemented by citation tracking and manual screening. Studies reporting genotype-phenotype correlations in β-TI were included. Data were synthesized qualitatively by geographic region.Results
Twenty-one studies were included. The available evidence suggests Mediterranean populations are primarily influenced by mild β-globin mutations. In Middle Eastern populations, HbF-inducing polymorphisms, particularly the XmnI variant, played a prominent role, often mitigating severe genotypes. Among the included studies, Asian populations exhibited the greatest molecular heterogeneity, with α-globin gene dosage alterations, including triplication, contributing substantially to disease expression.Conclusion
The available evidence suggests regional differences in the contribution of genetic modifiers to the β-thalassemia intermedia phenotype. Recognition of these patterns may improve understanding of genotype-phenotype variability and may help inform future approaches to diagnosis, prognostication, and individualized therapeutic strategies.
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BibTeX
@article{fernando2026genotypicphenotypic,
title = {{Genotypic-Phenotypic Correlations in Non-HbE β-Thalassemia Intermedia: A Geographic Systematic Review.}},
author = {Kavindya Fernando and Shiromi Perera and Anuja Premawardhena},
journal = {Molecular genetics \& genomic medicine},
year = {2026},
month = nov,
doi = {10.1002/mgg3.70330},
url = {https://europepmc.org/article/MED/42973095},
note = {CC BY},
}
RIS
TY - JOUR
TI - Genotypic-Phenotypic Correlations in Non-HbE β-Thalassemia Intermedia: A Geographic Systematic Review.
AU - Kavindya Fernando
AU - Shiromi Perera
AU - Anuja Premawardhena
PY - 2026
DA - 2026/11/01
JO - Molecular genetics & genomic medicine
DO - 10.1002/mgg3.70330
UR - https://europepmc.org/article/MED/42973095
AB - Background β-thalassemia intermedia (β-TI), now more commonly classified within the spectrum of non-transfusion-dependent thalassemia (NTDT), is a clinically heterogeneous disorder in which disease severity is determined not only by β-globin mutations but also by co-inherited genetic modifiers that vary across populations. These include α-globin gene alterations, fetal haemoglobin (HbF)-inducing polymorphisms, and other regulatory loci that influence globin chain balance.Methods A systematic review was conducted in accordance with PRISMA 2020 guidelines. PubMed was searched from inception to May 2026, supplemented by citation tracking and manual screening. Studies reporting genotype-phenotype correlations in β-TI were included. Data were synthesized qualitatively by geographic region.Results Twenty-one studies were included. The available evidence suggests Mediterranean populations are primarily influenced by mild β-globin mutations. In Middle Eastern populations, HbF-inducing polymorphisms, particularly the XmnI variant, played a prominent role, often mitigating severe genotypes. Among the included studies, Asian populations exhibited the greatest molecular heterogeneity, with α-globin gene dosage alterations, including triplication, contributing substantially to disease expression.Conclusion The available evidence suggests regional differences in the contribution of genetic modifiers to the β-thalassemia intermedia phenotype. Recognition of these patterns may improve understanding of genotype-phenotype variability and may help inform future approaches to diagnosis, prognostication, and individualized therapeutic strategies.
SN - 2324-9269
ER -