title: DNA methylation in PRDM8 is indicative for dyskeratosis congenita.
abstract: Dyskeratosis congenita (DKC) is associated with impaired telomere maintenance and with clinical features of premature aging. In this study, we analysed global DNA methylation (DNAm) profiles of DKC patients. Age-associated DNAm changes were not generally accelerated in DKC, but there were significant differences to DNAm patterns of healthy controls, particularly in CpG sites related to an internal promoter region of PR domain containing 8 (PRDM8). Notably, the same genomic region was also hypermethylated in aplastic anemia (AA) - another bone marrow failure syndrome. Site-specific analysis of DNAm level in PRDM8 with pyrosequencing and MassARRAY validated aberrant hypermethylation in 11 DKC patients and 27 AA patients. Telomere length, measured by flow-FISH, did not directly correlate with DNAm in PRDM8. Therefore the two methods may be complementary to also identify patients with still normal telomere length. In conclusion, blood of DKC patients reveals aberrant DNAm patterns, albeit age-associated DNAm patterns are not generally accelerated. Aberrant hypermethylation is particularly observed in PRDM8 and this may support identification and classification of bone marrow failure syndromes.
authors.affiliation: Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University Medical Faculty, Aachen, Germany.|Institute for Biomedical Technology - Cell Biology, RWTH University Medical School, Aachen, Germany.
authors.forename: Carola I
authors.initials: CI
authors.lastname: Weidner
authors.affiliation: Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University Medical Faculty, Aachen, Germany.|Institute for Biomedical Technology - Cell Biology, RWTH University Medical School, Aachen, Germany.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Varionostic GmbH, Ulm, Germany.
authors.forename: Carina
authors.initials: C
authors.lastname: Birkhofer
authors.affiliation: Varionostic GmbH, Ulm, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Gerstenmaier
authors.affiliation: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, RWTH Aachen University Medical Faculty, Aachen, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kaifie
authors.affiliation: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, RWTH Aachen University Medical Faculty, Aachen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Kirschner
authors.affiliation: Department of Internal Medicine 5-Hematology/Oncology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Bruns
authors.affiliation: Division of Hematology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Balabanov
authors.affiliation: Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Trummer
authors.affiliation: Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Stockklausner
authors.affiliation: Institute of Transfusion Medicine, University of Ulm, Ulm, Germany.|Institute of Clinical Transfusion Medicine and Immunogenetics, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm, Ulm, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Höchsmann
authors.affiliation: Institute of Transfusion Medicine, University of Ulm, Ulm, Germany.|Institute of Clinical Transfusion Medicine and Immunogenetics, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm, Ulm, Germany.
authors.forename: Hubert
authors.initials: H
authors.lastname: Schrezenmeier
authors.affiliation: Department of Pediatrics, Hematology and Oncology, University of Freiburg, Freiburg, Germany.
authors.forename: Marcin
authors.initials: M
authors.lastname: Wlodarski
authors.affiliation: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, RWTH Aachen University Medical Faculty, Aachen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Panse
authors.affiliation: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, RWTH Aachen University Medical Faculty, Aachen, Germany.
authors.forename: Tim H
authors.initials: TH
authors.lastname: Brümmendorf
authors.affiliation: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, RWTH Aachen University Medical Faculty, Aachen, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Beier
authors.affiliation: Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University Medical Faculty, Aachen, Germany.|Institute for Biomedical Technology - Cell Biology, RWTH University Medical School, Aachen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wagner
mesh_terms: D000741:Anemia, Aplastic / Q000235:genetics*; D001855:Bone Marrow Diseases / Q000235:genetics*; D000080983:Bone Marrow Failure Disorders; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D019175:DNA Methylation; D004268:DNA-Binding Proteins; D019871:Dyskeratosis Congenita / Q000235:genetics*; D044127:Epigenesis, Genetic; D006457:Hemoglobinuria, Paroxysmal / Q000235:genetics*; D000076983:Histone Methyltransferases; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000076983:Histone Methyltransferases; C576576:PRDM8 protein, human
keywords: DNA methylation; Gerotarget; aplastic anemia; bone marrow failure; dyskeratosis congenita; epigenetic