β-Thalassemia Mutation At Codon 37 (TGG>>TGA) Detected In A Turkish Family

Abstract

The β-globin gene mutation at codon 37 [TGG (Trp)→TGA (stop codon)] gives rise to a β0-thalassemia that was described first by Boehm et al. in 1986 in a Saudi Arabian family [1]. Thereafter, other nonsense codon 37 mutations have been reported [1,2,3,4]. Another mutation at codon 37 (TGG/TAG; tryptophan→stop codon) has also been reported previously [5,6]. Premature stop of translation results in a truncated protein and usually the phenotype of β-thalassemia major in homozygous individuals. We have found an example of the nonsense codon (TGG→TGA; Trp→Stop) in a Turkish family. We report 3 cases with 1 homozygous and 2 heterozygous mutations at codon 37 causing a premature stop codon. Human fetal hemoglobin is present in vivo as both an acetylated F1 (ααγγacetyl) form by the presence of acetyl groups at the NH2 termini of the γ chains and a nonacetylated F0 (ααγγ) form. The fraction of the total fetal hemoglobin in acetylated form (F1) is about 10%, a value similar to that reported previously for cord erythrocytes and mostly in newborns [7,8]. A 37-year-old female patient (case 1) was admitted to our hospital with symptoms of anemia and repeated blood transfusion dependence once a year. Her red blood cell count (RBC) was 4.34x1012/L, hemoglobin (Hb) was 97 g/L 9 g/L, mean corpuscular volume (MCV) was 69.1 fL (<80 fL), and mean corpuscular hemoglobin (MCH) was 22.4 pg (<27 pg ). Her hemoglobin subtypes were quantified by high-performance liquid chromatography and HbA was 0%