"Krüppeling" erythropoiesis: an unexpected broad spectrum of human red blood cell disorders due to KLF1 variants unveiled by genomic sequencing

Andrew Perkins, Xiangmin Xu, Douglas R. Higgs, George P. Patrinos, Lionel Arnaud, James J. Bieker and Sjaak Philipsen


Until recently our approach to the analysis of human genetic diseases has been to accurately phenotype patients and sequence the genes known to be associated with those phenotypes; for example, analysing the globin loci in cases of thalassemia. As sequencing has become increasingly accessible, a larger panel of genes is now analysed and whole exome/genome sequencing is applied in cases where no variants are found in the candidate genes. Using such approaches in patients with unexplained anemias, we have discovered that a broad range of hitherto unrelated human red cell disorders are caused by variants in KLF1, a master regulator of erythropoiesis, previously considered to be extremely rare causes of human genetic disease.

  • Submitted January 20, 2016.
  • Accepted February 9, 2016.