title: SMAD2 Mutations Are Associated with Arterial Aneurysms and Dissections.
abstract: We report three families with arterial aneurysms and dissections in which variants predicted to be pathogenic were identified in SMAD2. Moreover, one variant occurred de novo in a proband with unaffected parents. SMAD2 is a strong candidate gene for arterial aneurysms and dissections given its role in the TGF-β signaling pathway. Furthermore, although SMAD2 and SMAD3 probably have functionally distinct roles in cell signaling, they are structurally very similar. Our findings indicate that SMAD2 mutations are associated with arterial aneurysms and dissections and are in accordance with the observation that patients with pathogenic variants in genes encoding proteins involved in the TGF-β signaling pathway exhibit arterial aneurysms and dissections as key features.
authors.affiliation: Department of Clinical Genetics, Center for Connective Tissue Research, VU University Medical Center, Amsterdam, 1007, MB, The Netherlands.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Micha
authors.affiliation: Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Dong-Chuan
authors.initials: DC
authors.lastname: Guo
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, 2300, RC, The Netherlands.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Hilhorst-Hofstee
authors.affiliation: Department of Neurology, Erasmus Medical Centre, Rotterdam, 3000, CA, The Netherlands.
authors.forename: Fop
authors.initials: F
authors.lastname: van Kooten
authors.affiliation: Department of Clinical Genetics, Center for Connective Tissue Research, VU University Medical Center, Amsterdam, 1007, MB, The Netherlands.|Center for Biomedical Research, Faculty of Medicine, Diponegoro University, Semarang, Central Java, Indonesia.
authors.forename: Dian
authors.initials: D
authors.lastname: Atmaja
authors.affiliation: Department of Clinical Genetics, Center for Connective Tissue Research, VU University Medical Center, Amsterdam, 1007, MB, The Netherlands.|Department of Clinical Genetics, Academic Medical Center, Amsterdam, 1100, DD, The Netherlands.
authors.forename: Eline
authors.initials: E
authors.lastname: Overwater
authors.affiliation: Department of Clinical Genetics, Center for Connective Tissue Research, VU University Medical Center, Amsterdam, 1007, MB, The Netherlands.|Center for Biomedical Research, Faculty of Medicine, Diponegoro University, Semarang, Central Java, Indonesia.
authors.forename: Ferdy K
authors.initials: FK
authors.lastname: Cayami
authors.affiliation: Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Ellen S
authors.initials: ES
authors.lastname: Regalado
authors.affiliation: Department of Respiratory Medicine, Albert Schweitzer Hospital, Dordrecht, 3318, AT, The Netherlands.
authors.forename: René
authors.initials: R
authors.lastname: van Uffelen
authors.affiliation: Center for Molecular and Biomolecular Genetics (CMBI), Nijmegen, 6500, HB, The Netherlands.
authors.forename: Hanka
authors.initials: H
authors.lastname: Venselaar
authors.affiliation: Center for Biomedical Research, Faculty of Medicine, Diponegoro University, Semarang, Central Java, Indonesia.
authors.forename: Sultana M H
authors.initials: SM
authors.lastname: Faradz
authors.affiliation: Center for Molecular and Biomolecular Genetics (CMBI), Nijmegen, 6500, HB, The Netherlands.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Vriend
authors.affiliation: Department of Clinical Genetics, Center for Connective Tissue Research, VU University Medical Center, Amsterdam, 1007, MB, The Netherlands.
authors.forename: Marjan M
authors.initials: MM
authors.lastname: Weiss
authors.affiliation: Department of Clinical Genetics, Center for Connective Tissue Research, VU University Medical Center, Amsterdam, 1007, MB, The Netherlands.
authors.forename: Erik A
authors.initials: EA
authors.lastname: Sistermans
authors.affiliation: Department of Clinical Genetics, Center for Connective Tissue Research, VU University Medical Center, Amsterdam, 1007, MB, The Netherlands.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Maugeri
authors.affiliation: Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Dianna M
authors.initials: DM
authors.lastname: Milewicz
authors.affiliation: Department of Clinical Genetics, Center for Connective Tissue Research, VU University Medical Center, Amsterdam, 1007, MB, The Netherlands.
authors.forename: Gerard
authors.initials: G
authors.lastname: Pals
authors.affiliation: Department of Clinical Genetics, Center for Connective Tissue Research, VU University Medical Center, Amsterdam, 1007, MB, The Netherlands.
authors.forename: Fleur S
authors.initials: FS
authors.lastname: van Dijk
mesh_terms: D000328:Adult; D000483:Alleles; D000783:Aneurysm / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D000784:Aortic Dissection / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D001158:Arteries / Q000378:metabolism* / Q000473:pathology*; D019295:Computational Biology / Q000379:methods; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D009154:Mutation; D054730:Protein Interaction Domains and Motifs; D017422:Sequence Analysis, DNA; D051899:Smad2 Protein / Q000737:chemistry / Q000235:genetics*; D055815:Young Adult
chemical_list: D051899:Smad2 Protein
keywords: SMAD2; TGF-ß; aneurysm; dissection