BACKGROUND: β-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 β-Knossos codon27 (G→T) (βKnossos) allele in cis with the δ059 (-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 δ- and β-globin genes. RESULTS: We noted that heterozygous inheritance of the βKnossos mutation results in a mild β-thalassemia phenotype with a low level of HbA2 while homozygous leads to intermediate β-thalassemia with an atypical high performance liquid chromatogram showing a complete absence of HbA2 and HbF. Compound heterozygosity of the βKnossos with β0 codon39 (C→T) is identified in a Tunisian proband for the first time and gives rise to a mild phenotype. In both families, the δ0 codon59 (-A) and the βKnossos alleles were found to be associated with a single Mediterranean β-haplotype I similar to that observed in previous reports from Algeria, Egypt, Cyprus, and Turkey. CONCLUSIONS: The chromosome supporting the βKnossos and the δ0 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 β-thalassemia trait and the other has a normal HbA2 level associated with abnormal red cell indices becomes a necessity to avoid missing thalassemia carriers.
BACKGROUND: β-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 β-Knossos codon27 (G→T) (βKnossos) allele in cis with the δ059 (-A) mutation in thalassemia intermediapatients in Tunisia and Libya. METHODS: This identification was carried out by sequencing analysis of the whole coding regions of the δ- and β-globin genes. RESULTS: We noted that heterozygous inheritance of the βKnossos mutation results in a mild β-thalassemia phenotype with a low level of HbA2 while homozygous leads to intermediate β-thalassemia with an atypical high performance liquid chromatogram showing a complete absence of HbA2 and HbF. Compound heterozygosity of the βKnossos with β0 codon39 (C→T) is identified in a Tunisian proband for the first time and gives rise to a mild phenotype. In both families, the δ0 codon59 (-A) and the βKnossos alleles were found to be associated with a single Mediterranean β-haplotype I similar to that observed in previous reports from Algeria, Egypt, Cyprus, and Turkey. CONCLUSIONS: The chromosome supporting the βKnossos and the δ0 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 β-thalassemia trait and the other has a normal HbA2 level associated with abnormal red cell indices becomes a necessity to avoid missing thalassemia carriers.