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

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

Research output: Contribution to journalArticle

201 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)303-305
Number of pages3
JournalNature Genetics
Volume43
Issue number4
DOIs
StatePublished - Feb 2011

ASJC Scopus subject areas

  • Genetics

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    Simpson, M. A., Irving, M. D., Asilmaz, E., Gray, M. J., Dafou, D., Elmslie, F. V., Mansour, S., Holder, S. E., Brain, C. E., Burton, B. K., Kim, K. H., Pauli, R. M., Aftimos, S., Stewart, H., Kim, C. A., Holder-Espinasse, M., Robertson, S. P., Drake, W. M., & Trembath, R. C. (2011). Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss. Nature Genetics, 43(4), 303-305. https://doi.org/10.1038/ng.779