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

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.

• Authors: Michael A Simpson, 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
• Journal: Nature genetics (Nat Genet) Vol. 43 Issue 4 Pg. 303-5 (Mar 06 2011) ISSN: 1546-1718 [Electronic] United States
• PMID: 21378985 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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