Novel beta globin gene cluster rearrangements and deletions in the Maltese islands

Abstract

Introduction: Hb F Malta 1 and Hb Valletta are common haemoglobin variants found in the Maltese population, in strong linkage disequilibrium with each other. Genotype and phenotype analysis of Hb F Malta 1 newborn was performed to find rearrangements and deletions at the beta globin cluster. A case study of a deletional beta thalassaemia is also discussed. Methods: Two hundred and eighty-two Hb F Malta 1 newborn were enrolled in the study. A reverse phase HPLC was used for globin chain quantification. Multiple ligation probe analysis and qPCR were used detect deletions or duplications at the beta globin cluster. A case study of a female of Asian descent presenting with the phenotype of beta thalassemia trait is described. Since routine clinical testing failed to find a cause for the microcytic anaemia, the aforementioned techniques were used to look for atypical deletional beta thalassaemia. Results: Novel cases of newborn with broken linkage between Hb Valletta and Hb F Malta 1 were discovered, suggesting a higher rate of recombination events in this region. Gene conversion mutations, deletions and duplications at the gamma globin genes were discovered. In the case study, a large heterozygous deletion involving the beta globin gene and several downstream olfactory genes was found. Conclusion: The case study highlights the importance of alternative techniques for diagnostic testing in a population with increasing genetic heterogeneity. A larger study population has enabled the detection of rare rearrangements at the beta globin cluster and copy number variations can be detected with qPCR. Disclosures: The research was funded by the Endeavour Scholarship Scheme