δ0-Thalassemia in cis of βKnossos globin gene: first homozygous description in thalassemia intermedia Libyans and first combination with codon 39 (C→T) in thalassemia intermedia Tunisian patients

Background: beta-Thalassemia is the most common disease among hemoglobinopathies in North African and Arab populations. In the present study we report the first description of the beta-Knossos codon27 (G -> T) (beta(Knossos)) allele in cis with the delta(0)59 (-A) mutation in thalassemia intermedia patients in Tunisia and Libya. Methods: This identification was carried out by sequencing analysis of the whole coding regions of the delta- and beta-globin genes. Results: We noted that heterozygous inheritance of the beta(Knossos) mutation results in a mild beta-thalassemia phenotype with a low level of HbA(2) while homozygous leads to intermediate beta-thalassemia with an atypical high performance liquid chromatogram showing a complete absence of HbA(2) and HbF. Compound heterozygosity of the beta(Knossos) with beta(0)codon39 (C -> T) is identified in a Tunisian proband for the first time and gives rise to a mild phenotype. In both families, the delta(0) codon59 (-A) and the beta(Knossos) alleles were found to be associated with a single Mediterranean beta-haplotype I similar to that observed in previous reports from Algeria, Egypt, Cyprus, and Turkey. Conclusions: The chromosome supporting the beta(Knossos) and the delta(0) codon59 (-A) alleles seems to be of a single Mediterranean origin. Premarital screening studies in families in which only one of the parents has typical aspects of beta-thalassemia trait and the other has a normal HbA(2) level associated with abnormal red cell indices becomes a necessity to avoid missing thalassemia carriers.