2. Academic Validation
  3. Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss

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

Affiliation

  • 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.

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