Multiplex Ligation-Dependent Probe Amplification Identification of 17 Different β-Globin Gene Deletions (Including Four Novel Mutations) in the Uk Population

Abstract

Large deletions of the β-globin gene cluster are problematic to diagnose, and consequently the frequency and range of these mutations in the UK is unknown. Here we present a study evaluating the efficacy of the recently available technique of multiplex ligation-dependent prob amplification (MLPA) to determine the range and frequency of these deletions in the UK population. The results revealed a large deletion mutation in 75 of 316 patient samples collected over a 3-year period. Of these, 52 had a common (δβ)⁰-thalassemia [(δβ)⁰-thal] or hereditary persistence of fetal hemoglobin (HPFH) allele and 23 had rare or novel deletions resulting in (ε^Gγ^Aγδβ)⁰-thal, ^Gγ^Aγ(δβ)⁰-thal and β⁰-thal. A total of 17 different deletions were found, 10 of which were rare and four were most likely novel [Asian Indian (ε^Gγ^Aγδβ)⁰-thal, African (δβ)⁰-thal, African β⁰-thal and Afghanistani β⁰-thal]. The MLPA technique detected examples from all four categories of β-globin gene deletions and demonstrated the wide molecular basis of deletional β-thal/HPFH in UK patients.

Keywords:

• β-Globin gene cluster deletions
• Multiplex ligation-dependent probe amplification (MLPA) δβ-Thalassemia (δβ-thal)
• Hereditary persistence of fetal hemoglobin (HPFH)
• β-Thalassemia (β-thal)

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.