title: 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.
abstract: 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.
authors.affiliation: Biochemistry Laboratory, Research Laboratory LR00SP03”, Children’s Hospital, Tunis, Tunisia.
authors.forename: Chaima Abdelhafidh
authors.initials: CA
authors.lastname: Sahli
authors.forename: Amina
authors.initials: A
authors.lastname: Bibi
authors.forename: Faida
authors.initials: F
authors.lastname: Ouali
authors.forename: Hajer
authors.initials: H
authors.lastname: Siala
authors.forename: Sondess Hadj
authors.initials: SH
authors.lastname: Fredj
authors.forename: Rym
authors.initials: R
authors.lastname: Othmani
authors.forename: Fekria
authors.initials: F
authors.lastname: Ouenniche
authors.forename: Mondher
authors.initials: M
authors.lastname: Cheour
authors.forename: Zohra
authors.initials: Z
authors.lastname: Fitouri
authors.forename: Saida Ben
authors.initials: SB
authors.lastname: Becher
authors.forename: Taieb
authors.initials: T
authors.lastname: Messaoud
mesh_terms: D000328:Adult; D000483:Alleles; D001483:Base Sequence; D044383:Black People / Q000235:genetics*; D003062:Codon / Q000235:genetics*; D005260:Female; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008002:Libya; D008297:Male; D014416:Tunisia; D055544:beta-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000235:genetics*; D055538:delta-Thalassemia / Q000235:genetics*
chemical_list: D003062:Codon; D006455:Hemoglobins, Abnormal; D055544:beta-Globins; C036232:hemoglobin Knossos