Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss

  • Nat Genet. 2011 Mar 6;43(4):303-5. doi: 10.1038/ng.779.
Michael A Simpson  1 ,  Melita D Irving ,  Esra Asilmaz ,  Mary J Gray ,  Dimitra Dafou ,  Frances V Elmslie ,  Sahar Mansour ,  Sue E Holder ,  Caroline E Brain ,  Barbara K Burton ,  Katherine H Kim ,  Richard M Pauli ,  Salim Aftimos ,  Helen Stewart ,  Chong Ae Kim ,  Muriel Holder-Espinasse ,  Stephen P Robertson ,  William M Drake ,  Richard C Trembath
Affiliations
  • 1. Division of Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital, London, UK.
PMID: 21378985 DOI: 10.1038/ng.779
Abstract

We used an exome-sequencing strategy and identified an allelic series of NOTCH2 mutations in Hajdu-Cheney syndrome, an autosomal dominant multisystem disorder characterized by severe and progressive bone loss. The Hajdu-Cheney syndrome mutations are predicted to lead to the premature truncation of NOTCH2 with either disruption or loss of the C-terminal proline-glutamate-serine-threonine-rich proteolytic recognition sequence, the absence of which has previously been shown to increase Notch signaling.