title: CDKN1C mutations: two sides of the same coin.
abstract: Cyclin-dependent kinase (CDK)-inhibitor 1C (CDKN1C) negatively regulates cellular proliferation and it has been shown that loss-of-function mutations in the imprinted CDKN1C gene (11p15.5) are associated with the overgrowth disorder Beckwith-Wiedemann syndrome (BWS). With recent reports of gain-of-function mutations of the PCNA domain of CDKN1C in growth-retarded patients with IMAGe syndrome or Silver-Russell syndrome (SRS), its key role for growth has been confirmed. Thereby, the last gap in the spectrum of molecular alterations in 11p15.5 in growth-retardation and overgrowth syndromes could be closed. Recent functional studies explain the strict association of CDKN1C mutations with clinically opposite phenotypes and thereby contribute to our understanding of the function and regulation of the gene in particular and epigenetic regulation in general.
authors.affiliation: Institute of Human Genetics, University Hospital, Technical University Aachen, Aachen, Germany. Electronic address: teggermann@ukaachen.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Eggermann
authors.affiliation: University Children's Hospital, Paediatric Endocrinology, University of Tübingen, Tübingen, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Binder
authors.affiliation: AP-HP, Hôpital Armand Trousseau, Explorations Fonctionnelles Endocriniennes, Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Brioude
authors.affiliation: Department of Medical Genetics, University of Cambridge, Cambridge, UK; NIHR Cambridge Biomedical Research Centre, Cambridge, UK.
authors.forename: Eamonn R
authors.initials: ER
authors.lastname: Maher
authors.affiliation: INGEMM, Instituto de Genética Médica y Molecular, Hospital Universitario La Paz, IdiPAZ, CIBERER-ISCIII, Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Lapunzina
authors.affiliation: Dipartimento di Biologia, Università Federico II, Napoli, Italy.
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Cubellis
authors.affiliation: Centro de Investigaciones Endocrinológicas 'Dr César Bergadá' (CEDIE), CONICET-FEI-División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Bergadá
authors.affiliation: Molekulare Pädiatrie, Zentrum für Kinder- und Jugendmedizin, Universitätsmedizin Mainz, Mainz, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Prawitt
authors.affiliation: Institute of Human Genetics, University Hospital, Technical University Aachen, Aachen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Begemann
mesh_terms: D000309:Adrenal Insufficiency / Q000175:diagnosis / Q000235:genetics; D000818:Animals; D001506:Beckwith-Wiedemann Syndrome / Q000175:diagnosis / Q000235:genetics; D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics*; D019468:Disease Management; D005317:Fetal Growth Retardation / Q000175:diagnosis / Q000235:genetics; D056726:Genetic Association Studies; D005817:Genetic Counseling; D018392:Genomic Imprinting; D006801:Humans; D009154:Mutation; D010009:Osteochondrodysplasias / Q000175:diagnosis / Q000235:genetics; D014564:Urogenital Abnormalities / Q000175:diagnosis / Q000235:genetics
chemical_list: C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57
keywords: Beckwith–Wiedemann syndrome; CDKN1C; IMAGE syndrome; Silver–Russell syndrome; imprinting; point mutations.