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.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Base Sequence
  • DNA Mutational Analysis
  • DNA, Complementary / genetics
  • Exons
  • Female
  • Hajdu-Cheney Syndrome / genetics*
  • Hajdu-Cheney Syndrome / metabolism
  • Hajdu-Cheney Syndrome / pathology
  • Humans
  • Male
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Mutation*
  • Pedigree
  • Protein Sorting Signals / genetics
  • Receptor, Notch2 / genetics*
  • Receptor, Notch2 / metabolism


  • DNA, Complementary
  • Mutant Proteins
  • NOTCH2 protein, human
  • Protein Sorting Signals
  • Receptor, Notch2

Associated data

  • RefSeq/NM_024408
  • RefSeq/NP_077719