Detection of Krupple Like Factor -1(KLF1/ EKLF) DNA Mutations in Beta Thalassemia Patients

Thalassemias are inherited abnormalities in globin chain synthesis of hemoglobin and one of the most common single gene disorders in the world.

β-Thalassemia is caused by reduced (β+) or absent (β0) synthesis of the β-globin chains of haemoglobin. Three clinical and hematological conditions of increasing severity are recognized: the β-thalassemia trait, thalassemia intermedia and thalassemia major.

The Erythroid Kruppel-like factor (EKLF or KLF1) is a master regulator of terminal erythroid differentiation, controlling expression of many key pathways and structures including cell division, the cell membrane and cytoskeleton, heme and globin synthesis.

The KLF1 works as a key regulator of γ-globin to β-globin switch by up-regulation of PUM1 that binds to fetal γ globin mRNA impairing its stability and translation and by Bcl11a expression that represses γ-globin expression.

Previous studies reported that KLF1 mutations have been identified in a variety of erythroid conditions like hereditary persistence of fetal hemoglobin, Congenital dyserythropoietic anemia and borderline HbA2.

An Indian study on KLF1 gene variations found a marginal significance in the thalassemia intermedia group (14%) as against the thalassemia major group (2.0%).

Also, a case report on a Chinese family with twin brothers, both of whom had the same genotype of β0/β0, reported that KLF1 mutations have a role in modulating the phenotypic severity of β-thalassemia.

In our study, where there is high incidence of beta thalassemia in Egypt, we try to detect KLF1 mutations and its relation to clinical phenotype of these patients.

Inclusion criteria

• Patients with β-thalassemia (intermedia and major) of both genders at any age

Exclusion criteria

• Patients with any other type of haemolytic anaemias.
• Patients on Hydroxyurea therapy