CDKN1C mutations: two sides of the same coin

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


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..

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adrenal Insufficiency / diagnosis
  • Adrenal Insufficiency / genetics
  • Animals
  • Beckwith-Wiedemann Syndrome / diagnosis
  • Beckwith-Wiedemann Syndrome / genetics
  • Chromosome Aberrations
  • Chromosomes, Human, Pair 11
  • Cyclin-Dependent Kinase Inhibitor p57 / genetics*
  • Disease Management
  • Fetal Growth Retardation / diagnosis
  • Fetal Growth Retardation / genetics
  • Genetic Association Studies*
  • Genetic Counseling
  • Genomic Imprinting
  • Humans
  • Mutation*
  • Osteochondrodysplasias / diagnosis
  • Osteochondrodysplasias / genetics
  • Urogenital Abnormalities / diagnosis
  • Urogenital Abnormalities / genetics


  • CDKN1C protein, human
  • Cyclin-Dependent Kinase Inhibitor p57

Supplementary concepts

  • Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, And Genital Anomalies