title: Spectrum of Beta Globin Gene Mutations in Egyptian Children with β-Thalassemia.
abstract: BACKGROUND
  The molecular defects resulting in a β-thalassemia phenotype, in the Egyptian population, show a clear heterogenic mutations pattern. PCR-based techniques, including direct DNA sequencing are effective on the molecular detection and characterization of these mutations. The molecular characterization of β-thalassemia is necessary for carrier screening, genetic counseling, and to offer prenatal diagnosis.
  
  
  OBJECTIVE
  was to evaluate the different β-globin gene mutations in two hundred β-thalassemic Egyptian children.
  
  
  METHODS
  This study was carried out on two hundred β-thalassemic Egyptian children covering most Egyptian Governorates including 158 (79%) children with thalassemia major (TM) and 42 (21%) children with thalassemia intermedia(TI). All patients were subjected to meticulous history taking, clinical examination, complete blood count, hemoglobin electrophoresis, serum ferritin and direct fluorescent DNA sequencing of the β-globin gene to detect the frequency of different mutations.
  
  
  RESULTS
  The most common mutations among patients were IVS I-110(G>A) 48%, IVS I-6(T>C) 40%, IVS I-1(G>A) 24%, IVS I-5(G>C)10%, IVS II-848 (C>A) 9%, IVS II-745(C>G) 8%, IVS II-1(G>A) 7%, codon "Cd"39(C> T) 4%, -87(C>G) 3% and the rare mutations were: Cd37 (G>A), Cd8 (-AA), Cd29(-G), Cd5 (-CT), Cd6(-A), Cd8/9(+G), Cd 106/107(+G), Cd27(C>T), IVS II-16(G> C), Cd 28 (-C), Cap+1(A>C), -88(C>A), all of these rare mutations were present in 1%. There was a considerable variation in phenotypic severity among patients resulting from the interaction of different β(∘) and β+mutations. Furthermore, no genotype-phenotype association was found both among the cases with thalassemia major and the cases with thalassemia intermedia.
  
  
  CONCLUSIONS
  Direct DNA sequencing provides insights for the frequency of different mutations in patients with β-thalassemia including rare and/or unknown ones. The most common mutations in Egyptian children with beta thalassemia were IVS I-110(G>A) 48%, IVS I-6(T>C) 40%, IVS I-1(G>A)24%, IVS I-5(G>C)10%, IVS II-848 (C>A) 9%, IVS II-745(C>G) 8%, IVS II-1(G>A) 7%.
authors.affiliation: Pediatric Department, Tanta University, Egypt.
authors.forename: Mr
authors.initials: M
authors.lastname: El-Shanshory
authors.affiliation: Pediatric Department, Tanta University, Egypt.
authors.forename: Aa
authors.initials: A
authors.lastname: Hagag
authors.affiliation: Pediatric Department, Tanta University, Egypt.
authors.forename: Ss
authors.initials: S
authors.lastname: Shebl
authors.affiliation: Pediatric Department, Tanta University, Egypt.
authors.forename: Im
authors.initials: I
authors.lastname: Badria
authors.affiliation: Clinical Pathology Department, Tanta University, Egypt.
authors.forename: Ah
authors.initials: A
authors.lastname: Abd Elhameed
authors.affiliation: Clinical Pathology Department, Tanta University, Egypt.
authors.forename: Es
authors.initials: E
authors.lastname: Abd El-Bar
authors.affiliation: Pediatric Departments of Mansoura University.
authors.forename: Y
authors.initials: Y
authors.lastname: Al-Tonbary
authors.affiliation: Pediatric Departments of Mansoura University.
authors.forename: A
authors.initials: A
authors.lastname: Mansour
authors.affiliation: Pediatric Departments of Alexandria University.
authors.forename: H
authors.initials: H
authors.lastname: Hassab
authors.affiliation: Pediatric Departments of Cairo University.
authors.forename: M
authors.initials: M
authors.lastname: Hamdy
authors.affiliation: Pediatric Departments of Ain Shams University.
authors.forename: M
authors.initials: M
authors.lastname: Alfy
authors.affiliation: Pediatric Departments of Zagazeg University.
authors.forename: L
authors.initials: L
authors.lastname: Sherief
authors.affiliation: Pediatric Departments of Sohag University.
authors.forename: E
authors.initials: E
authors.lastname: Sharaf