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.
- red blood cell disorders
Perkins, A., Xu, X., Higgs, D., Patrinos, G. P., Arnaud, L., Bieker, J. J., Philipsen, S., & KLF1 Consensus Workgroup (2016). Krüppeling erythropoiesis: an unexpected broad spectrum of human red blood cell disorders due to KLF1 variants. Blood, 127(15), 1856-1862. https://doi.org/10.1182/blood-2016-01-694331