Spectrum of Beta Globin Gene Mutations in Egyptian Children with β-Thalassemia

Mr El-Shanshory; Aa Hagag; Ss Shebl; Im Badria; Ah Abd Elhameed; Es Abd El-Bar; Y Al-Tonbary; A Mansour; H Hassab; M Hamdy; M Alfy; L Sherief; E Sharaf

doi:10.4084/MJHID.2014.071

Spectrum of Beta Globin Gene Mutations in Egyptian Children with β-Thalassemia

Mediterr J Hematol Infect Dis. 2014 Nov 1;6(1):e2014071. doi: 10.4084/MJHID.2014.071. eCollection 2014.

Authors

Mr El-Shanshory¹, Aa Hagag¹, Ss Shebl¹, Im Badria¹, Ah Abd Elhameed², Es Abd El-Bar², Y Al-Tonbary³, A Mansour³, H Hassab⁴, M Hamdy⁵, M Alfy⁶, L Sherief⁷, E Sharaf⁸

Affiliations

¹ Pediatric Department, Tanta University, Egypt.
² Clinical Pathology Department, Tanta University, Egypt.
³ Pediatric Departments of Mansoura University.
⁴ Pediatric Departments of Alexandria University.
⁵ Pediatric Departments of Cairo University.
⁶ Pediatric Departments of Ain Shams University.
⁷ Pediatric Departments of Zagazeg University.
⁸ Pediatric Departments of Sohag University.

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.

The aim of the work: was to evaluate the different β-globin gene mutations in two hundred β-thalassemic Egyptian children.

Subjects and 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.

Conclusion: 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%.