Molecular and haematological characterisation of haemolytic anaemia associated with biallelic KLF1 mutations: a case series.

Aims: Krüppel-like factor 1 (KLF1) is an erythroid-specific transcription factor playing an important role in erythropoiesis and haemoglobin (Hb) switching. Biallelic KLF1 mutations can cause haemolytic anaemia with thalassaemia-like syndromes but are rarely reported. We explore the KLF1 mutations in Thai subjects with unexplainable haemolytic anaemia.

Methods: The study was done on 57 subjects presented with haemolytic anaemia and elevated Hb F without β-thalassaemia diseases. Hb analysis was performed using capillary electrophoresis. Analyses of α-thalassaemia, β-thalassaemia and KLF1 genes were performed using PCR-based methods and DNA sequencing.

Results: Thirteen subjects with compound heterozygous for a known and five new genetic KLF1 interactions were identified, including KLF1:c.519_525dupCGGCGCC/c.892G>C with class 3/2 (n=8), and each subject with new genetic interaction, including KLF1:c.-154C>T;643C>T/c.983G>A with class 3/2, KLF1:c.-154C>T;643C>T/c.809C>G with class 3/2, KLF1:c892G>C/c.983G>A with class 2/2, KLF1:c.892G>C/c.1001C>G with class 2/2 and KLF1:c.1001C>G/c.1003G>A with class 2/2. Most of them had anaemia with Hb levels ranging from 45 to 110 g/L, hypochromic microcytosis, aniso-poikilocytosis, increased Hb F levels (17.9%-47.4%), small amounts of Hb Bart's, regular blood transfusion, hyperbilirubinaemia, increased serum ferritin and nucleated red blood cell.

Conclusions: Biallelic KLF1 mutations associated with anaemia may not be uncommon in Thailand. Characteristics of haemolytic anaemia, abnormal red cell morphology with nucleated red blood cells and elevated Hb F, and presenting small amounts of Hb Bart's without thalassaemia diseases are useful markers to further investigation of the KLF1 gene.