A novel mutation in the erythroid transcription factor KLF1 is likely responsible for ameliorating β-thalassemia major.

ABSTRACT: We describe the identification of a novel missense mutation in the second zinc finger of KLF1 in two siblings who, based on their genotype, are predicted to suffer from beta thalassemia major but are, in fact, transfusion-free and in good health. These individuals, as well as two additional members of the same family also carrying this KLF1 mutation, exhibit high levels of fetal hemoglobin (HbF). KLF1 is an erythroid transcription factor, which plays a critical role in the regulation of the developmental switch between fetal and adult hemoglobin by regulating the expression of a multitude of genes including that of BCL11A. The mutation appears to be the main candidate responsible for the beta thalassemia-ameliorating effect as this segregates with the observed phenotype and also exogenous

SUBMITTER: Fanis P 

PROVIDER: S-EPMC6790707 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature