title: Molecular basis of β-thalassemia in the United Arab Emirates.
abstract: In an attempt to define the prevalence of β-thalassemia (β-thal) in the United Arab Emirates (UAE), we have conducted molecular studies on nearly 2000 randomly-selected adult UAE nationals. The results demonstrated that the prevalence of β-globin gene defects in the UAE was 8.5%. Among these anomalies were β-thal mutations, abnormal hemoglobin (Hb) variants, e.g., Hb S, Hb D-Punjab, Hb O-Arab, Hb C and Hb E. The sickle gene (β(S) or Hb S) contributed significantly to the molecular epidemiology of the hemoglobinopathies in the UAE. In this article, Hb S and other abnormal Hbs are excluded as they are comprehensively described by other contributors in this current issue. The molecular characterization and mutational analyses of all β-thal patients were carried out using current molecular techniques including amplification refractory mutation system (ARMS), restriction enzyme analysis (REA), dot-blot hybridization, β-strip hybridization, allele-specific oligonucleotide (ASO), polymerase chain reaction (PCR), gap-PCR and DNA Sequencing. Most of these techniques are now virtually obsolete. Almost all molecular characterizations are currently performed through PCR followed by DNA sequencing using a fully automated ABI PRISM™ 3130 Genetic Analyzer. Our molecular studies showed that the majority of the β-thal mutations in the UAE are very severe; the most common allele was the IVS-I-5 (G>C). Although this allele is a β(+)-thal, its phenotype is very severe. All other mutations are also severe β(0)-thal. High frequency of moderate or severe β-thal mutations have implications in the wide spectrum of clinical manifestations seen in patients whose phenotypes vary from β-thal intermedia (β-TI) to severe transfusion-dependent β-thal major (β-TM). The molecular pathology of the β-thal patients demonstrated that a vast majority were homozygous. The most frequent homozygous mutation was the IVS-I-5(G>C)/IVS-I-5(G>C) (53.0%) followed by -25 bp del/-25 bp del (6.8%), codons 8/9(+G)/codons 8/9(+G) (2.8%) and codon 39(C>T)/codon 39(C>T) (2.4%). Four mutations accounted for 65.0% of the homozygous patient population. Remarkably, the two most prevalent mutations, IVS-I-5 and Hb S, accounted for 77% of all the homozygous β-thal patients from the UAE. We showed 13 discrete homozygosities in the UAE national patients in contrast to 23 homozygosities in the expatriate population. Since the number of homozygous mutations has a direct correlation with the degree of consanguinity, the data shown here corroborate the social tendency towards family planning. In fact, in the UAE, more than 50% of all marriages are between relatives and more than half of these are between first cousins.
authors.affiliation: Pathology and Genetics Department, Dubai Genetic and Thalassemia Center, Dubai Health Authority, United Arab Emirates. ebaysal@dha.gov.ae
authors.forename: Erol
authors.initials: E
authors.lastname: Baysal
mesh_terms: D005787:Gene Frequency; D018740:Genetic Heterogeneity; D006720:Homozygote; D006801:Humans; D059645:Mutation Rate; D015995:Prevalence; D000091402:Prohibitins; D014479:United Arab Emirates / Q000453:epidemiology; D055544:beta-Globins / Q000235:genetics; D017086:beta-Thalassemia / Q000453:epidemiology / Q000235:genetics*
chemical_list: C000717331:PHB2 protein, human; D000091402:Prohibitins; D055544:beta-Globins