Characterization of a Novel Deletion Causing β-Thalassemia Major in an Afghan Family

Abstract

We have identified and characterized a novel β-globin gene deletion mutation in a family of Afghan ancestry. The proband was a 10-year-old transfusion-dependent female with the phenotype of β-thalassemia major (β-TM). DNA sequencing of the β-globin gene showed no abnormalities. Multiplex ligation-dependent probe amplification (MLPA) showed reduced/absent probe height of the probe covering the 5′ end of the β-globin gene indicating a possible deletion. Gap-polymerase chain reaction (gap-PCR) produced junctional fragments and direct sequencing of the product revealed that the 5′ breakpoint was 478 nucleotides upstream of the Cap site and the 3′ breakpoint was in the second exon of the β-globin gene, giving a deletion size of 909 bp. The proband was homozygous and the parents were heterozygous for the deletion. This is the first report of a large β-thalassemia (β-thal) deletion mutation in this ethnic group.

Keywords:

• β-Globin gene deletion
• β-Thalassemia (β-thal)
• Multiplex ligation-dependent probe amplification (MLPA)
• Gap-polymerase chain reaction (gap-PCR)
• Afghanistan

ACKNOWLEDGMENTS

These investigations were supported by the European Commission grant for the project “Infrastructure for Thalassaemia Research Network,” Co-ordination Action, ITHANET, RI-2004-026539, and also by the Oxford Partnership Comprehensive Biomedical Research Centre, Oxford, UK, with funding from the Department of Health's National Institute for Health Research Biomedical Research Centres (in London, Oxford, Cambridge, Liverpool, Manchester and Newcastle) funding scheme. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health.

Declaration of Interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.