title: Krüppeling erythropoiesis: an unexpected broad spectrum of human red blood cell disorders due to KLF1 variants.
abstract: Until recently our approach to analyzing human genetic diseases has been to accurately phenotype patients and sequence the genes known to be associated with those phenotypes; for example, in thalassemia, the globin loci are analyzed. Sequencing has become increasingly accessible, and thus a larger panel of genes can be analyzed and whole exome and/or whole genome sequencing can be used when no variants are found in the candidate genes. By 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, which were previously considered to be extremely rare causes of human genetic disease.
authors.affiliation: Mater Research Institute, University of Queensland, Woolloongabba, Australia;
authors.forename: Andrew
authors.identifier: http://orcid.org/0000-0003-3644-7093
authors.initials: A
authors.lastname: Perkins
authors.affiliation: Southern Medical University and Guangdong Genetic Testing Engineering Research Center, Guangzhou, China;
authors.forename: Xiangmin
authors.identifier: http://orcid.org/0000-0003-2775-8228
authors.initials: X
authors.lastname: Xu
authors.affiliation: Weatherall Institute of Molecular Medicine, Oxford, United Kingdom;
authors.forename: Douglas R
authors.identifier: http://orcid.org/0000-0003-3579-8705
authors.initials: DR
authors.lastname: Higgs
authors.affiliation: Department of Pharmacy, University of Patras, Patras, Greece;
authors.forename: George P
authors.identifier: http://orcid.org/0000-0002-0519-7776
authors.initials: GP
authors.lastname: Patrinos
authors.affiliation: Department of Biology, University of Vermont, Burlington, VT;
authors.forename: Lionel
authors.initials: L
authors.lastname: Arnaud
authors.affiliation: Mount Sinai School of Medicine, New York, NY; and.
authors.forename: James J
authors.initials: JJ
authors.lastname: Bieker
authors.affiliation: Department of Cell Biology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Sjaak
authors.identifier: http://orcid.org/0000-0002-3690-1201
authors.initials: S
authors.lastname: Philipsen
mesh_terms: D000743:Anemia, Hemolytic / Q000235:genetics; D000818:Animals; D001789:Blood Group Antigens; D004912:Erythrocytes / Q000166:cytology*; D004920:Erythropoiesis / Q000235:genetics*; D059472:Exome; D017353:Gene Deletion; D005786:Gene Expression Regulation; D014644:Genetic Variation; D006418:Heme / Q000737:chemistry; D006453:Hemoglobinopathies / Q000235:genetics; D006801:Humans; D015160:Hydrops Fetalis / Q000235:genetics; D007501:Iron / Q000737:chemistry; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D051379:Mice; D010641:Phenotype; D017434:Protein Structure, Tertiary; D011770:Pyruvate Kinase / Q000172:deficiency; D017422:Sequence Analysis, DNA; D055544:beta-Globins / Q000235:genetics
chemical_list: D001789:Blood Group Antigens; D051741:Kruppel-Like Transcription Factors; D055544:beta-Globins; C080774:erythroid Kruppel-like factor; D006418:Heme; D007501:Iron; D011770:Pyruvate Kinase