Genetic modifiers of beta-thalassemia

Department of Haematological Medicine, Guy's, King's & St. Thomas' School of Medicine King's College London, Denmark Hill Campus, Bessemer Road, London SE5 9PJ, UK. sl.thein@kcl.ac.uk

As the defective genes for more and more genetic disorders become unravelled, it is clear that patients with apparently identical genotypes can have many different clinical conditions even in simple monogenic disorders. Beta thalassemia occurs when there is a deficiency in the synthesis of beta globin chains. The clinical manifestations of beta thalassemia are extremely diverse, spanning a broad spectrum from severe anemia and transfusion-dependency to the asymptomatic state of thalassemia trait. The remarkable phenotypic diversity of the beta thalassemias is prototypical of how a wide spectrum of disease severity can be generated in single gene disorders. The most reliable and predictive factor of disease phenotype is the nature of the mutation at the beta globin locus itself. However, relating phenotype to genotype is complicated by the complex interaction of the environment and other genetic factors at the secondary and tertiary levels, some implicated from family studies, and others, as yet unidentified. This article reviews the clinical and hematologic diversity encountered in beta thalassemia with an overview of the modifier genes that moderate their disease expression.

This article has been cited by other articles:

				A Mosca, R Paleari, G Ivaldi, R Galanello, and P C Giordano The role of haemoglobin A2 testing in the diagnosis of thalassaemias and related haemoglobinopathies J. Clin. Pathol., January 1, 2009; 62(1): 13 - 17. [Abstract] [Full Text] [PDF]

				H. P. J. Voon, H. Wardan, and J. Vadolas siRNA-mediated reduction of {alpha}-globin results in phenotypic improvements in {beta}-thalassemic cells Haematologica, August 1, 2008; 93(8): 1238 - 1242. [Abstract] [Full Text] [PDF]

				K. Sleegers, N. Brouwers, S. Maurer-Stroh, M. A. van Es, P. V. Damme, P.W.J. van Vught, J. van der Zee, S. Serneels, T. D. Pooter, M. Van den Broeck, et al. Progranulin genetic variability contributes to amyotrophic lateral sclerosis Neurology, July 22, 2008; 71(4): 253 - 259. [Abstract] [Full Text] [PDF]