A Krüppel-Like Factor 1 Gene Mutation Ameliorates the Severity of β-Thalassemia: A Case Report

Abstract

Patients with the β⁰/β⁰ type of β-thalassemia (β-thal) usually present as β-thal major (β-TM), and are transfusion-dependent. However, the clinical and hematological features of β-thal can be modulated by different modifiers, resulting in a wide range of clinical severity even in patients with the same genotypes. We report a Chinese family with twin brothers, both of whom had the same genotype of β⁰/β⁰. One twin was diagnosed as β-TM at 4 months of age and had regularly been transfused; conversely the other twin with a KLF1 (Krüppel-like factor 1) gene mutation, behaved as β-thal intermedia (β-TI), and had never been transfused. Our findings indicate that KLF1 mutations have a role in modulating the phenotypic severity of β-thal. The exact investigation of KLF1 modifiers is necessary in areas where globin gene disorders are most prevalent. This will be helpful in genetic counseling and optimizing the guidelines for prenatal diagnosis (PND) programs.

Keywords:

• Fetal hemoglobin (Hb F)
• genotype/phenotype correlation
• Krüppel-like factor 1 (KLF1) gene
• modifier

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.