258 T) with increased hemoglobin A2" style="color:#4d5156" target="_blank"> T) with increased hemoglobin A2" style="color:#4d5156" target="_blank"> T) with increased hemoglobin A2" style="color:#4d5156" target="_blank">

"Silent" ?-thalassemia mutation (promoter nt-101 C > T) with increased hemoglobin A2

Aslan D. "Silent" ?-thalassemia mutation (promoter nt-101 C > T) with increased hemoglobin A2. Turk J Pediatr 2016; 58: 305-308.One of the most common silent ?-thalassemia mutations is the C > T substitution at position -101 within the distal CACCC box, which leads to a mild reduction in the expression level of the ?-globin gene. Carriers of this mutation have a normal hematologic picture without microcytosis and borderline hemoglobin A2 values, and may be missed during screening. Cooccurrence of this mutation with one of the classical ?-thalassemia mutations leads to ?-thalassemia intermedia, and this is important for Mediterranean populations where ?-thalassemia is frequent. Awareness of this mutation, which may have a heterogeneous clinical presentation, is required. We herein present the unusual hematologic findings of a Turkish family carrying this mutation.

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1. Higgs DR, Engel JD, Stamatoyannopoulos G. Thalassaemia. Lancet 2012; 379: 373-383.
2. Cao A, Galanello R. Beta-thalassemia. Genet Med 2010; 12: 61-76.
3. Van Vranken M. Evaluation of microcytosis. Am Fam Physician 2010; 82: 1117-1122.
4. DeLoughery TG. Microcytic anemia. N Engl J Med 2014; 371: 1324-1331.
5. Clarke GM, Higgins TN. Laboratory investigation of hemoglobinopathies and thalassemias: review and update. Clin Chem 2000; 46: 1284-1290.
6. Ip HW, So CC. Diagnosis and prevention of thalassemia. Crit Rev Clin Lab Sci 2013; 50: 125-141.
7. Gonzalez-Redondo JM, Stoming TA, Kutlar A, et al. A C----T substitution at nt--101 in a conserved DNA sequence of the promotor region of the beta-globin gene is associated with "silent" beta-thalassemia. Blood 1989; 73: 1705-1711.
8. Galanello R, Barella S, Ideo A, et al. Genotype of subjects with borderline hemoglobin A2 levels: implication for beta-thalassemia carrier screening. Am J Hematol 1994; 46: 79-81.
9. Perseu L, Satta S, Moi P, et al. KLF1 gene mutations cause borderline HbA(2). Blood 2011; 118: 4454-4458.
10. Aslan D. Automated blood counts and identification of thalassemia carriers. J Postgrad Med 2008; 54: 242- 243.
11. Moi P, Faà V, Marini MG, et al. A novel silent betathalassemia mutation in the distal CACCC box affects the binding and responsiveness to EKLF. Br J Haematol 2004; 126: 881-884.
12. Panigrahi I, Rafeeq PH, Choudhry VP, Saxena R. High frequency of deletional alpha-thalassemia in betathalassemia trait: implications for genetic counseling. Am J Hematol 2004; 76: 297-299.
13. Maragoudaki E, Kanavakis E, Traeger-Synodinos J, et al. Molecular, haematological and clinical studies of the -101 C --> T substitution of the beta-globin gene promoter in 25 beta-thalassaemia intermedia patients and 45 heterozygotes. Br J Haematol 1999; 107: 699- 706.
14. Rund D, Oron-Karni V, Filon D, et al. Genetic analysis of beta-thalassemia intermedia in Israel: diversity of mechanisms and unpredictability of phenotype. Am J Hematol 1997; 54: 16-22.