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Molecular and haematological characterisation of haemolytic anaemia associated with biallelic KLF1 mutations: a case series
  1. Kritsada Singha1,2,
  2. Nattiya Teawtrakul3,
  3. Goonnapa Fucharoen2,
  4. Supan Fucharoen2
  1. 1Faculty of Medicine, Mahasarakham University, Mahasarakham, Thailand
  2. 2Centre for Research & Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand
  3. 3Division of Hematology, Department of Internal Medicine, Khon Kaen University, Khon Kaen, Thailand
  1. Correspondence to Dr Supan Fucharoen, Centre for Research & Development of Medical Diagnostic Laboratories, Khon Kaen University, Nai Mueang 40002, Thailand; supan{at}; Dr Kritsada Singha, Faculty of Medicine, Mahasarakham University, Mahasarakham, Thailand;{at}


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.

  • anemia, hemolytic
  • diagnosis
  • DNA
  • genetics
  • hematologic diseases

Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.

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  • Handling editor Vikram Deshpande.

  • Contributors KS, GF and SF discussed the planning. KS performed the analysis of specimens, analysed the data and developed the initial manuscript. NT helped clinical data acquisition of the patients. GF performed data analysis and interpretation of the cases. SF supervised results interpretation, designed and facilitated the study, acquired a research grant and critically revised and approved the final manuscript. SF is the guarantor who is responsible to the overall content and takes full responsibility of the study. All authors approved the final submitted version.

  • Funding This study was financially supported by the Thailand Research Fund (TRF) Research Team Promotion Grant (RTA) of the Thailand Science Research and Innovation (TSRI), Thailand to SF (Contract ID RTA6280005) and Faculty of Medicine, Mahasarakham University, Mahasarakham and Thailand Science Research and Innovation (TSRI) (Contract ID FF-660622/2566) to KS.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.