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Trends Mol Med. 2014 Nov;20(11):614-22. doi: 10.1016/j.molmed.2014.09.001. Epub 2014 Sep 25.

CDKN1C mutations: two sides of the same coin.

Author information

1
Institute of Human Genetics, University Hospital, Technical University Aachen, Aachen, Germany. Electronic address: teggermann@ukaachen.de.
2
University Children's Hospital, Paediatric Endocrinology, University of Tübingen, Tübingen, Germany.
3
AP-HP, Hôpital Armand Trousseau, Explorations Fonctionnelles Endocriniennes, Paris, France.
4
Department of Medical Genetics, University of Cambridge, Cambridge, UK; NIHR Cambridge Biomedical Research Centre, Cambridge, UK.
5
INGEMM, Instituto de Genética Médica y Molecular, Hospital Universitario La Paz, IdiPAZ, CIBERER-ISCIII, Madrid, Spain.
6
Dipartimento di Biologia, Università Federico II, Napoli, Italy.
7
Centro de Investigaciones Endocrinológicas 'Dr César Bergadá' (CEDIE), CONICET-FEI-División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina.
8
Molekulare Pädiatrie, Zentrum für Kinder- und Jugendmedizin, Universitätsmedizin Mainz, Mainz, Germany.
9
Institute of Human Genetics, University Hospital, Technical University Aachen, Aachen, Germany.

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.

KEYWORDS:

Beckwith–Wiedemann syndrome; CDKN1C; IMAGE syndrome; Silver–Russell syndrome; imprinting; point mutations.

PMID:
25262539
DOI:
10.1016/j.molmed.2014.09.001
[Indexed for MEDLINE]

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