2. Academic Validation
  3. Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis

Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis

  • Nat Genet. 2011 Mar 6;43(4):306-8. doi: 10.1038/ng.778.
Bertrand Isidor 1,  Pierre Lindenbaum,  Olivier Pichon,  Stéphane Bézieau,  Christian Dina,  Sébastien Jacquemont,  Dominique Martin-Coignard,  Christel Thauvin-Robinet,  Martine Le Merrer,  Jean-Louis Mandel,  Albert David,  Laurence Faivre,  Valérie Cormier-Daire,  Richard Redon,  Cédric Le Caignec
Affiliations

Affiliation

  • 1 CHU Nantes, Service de Génétique Médicale, Nantes, France.
PMID: 21378989 DOI: 10.1038/ng.778
Abstract

Hajdu-Cheney syndrome is a rare autosomal dominant skeletal disorder with facial anomalies, osteoporosis and acro-osteolysis. We sequenced the exomes of six unrelated individuals with this syndrome and identified heterozygous nonsense and frameshift mutations in NOTCH2 in five of them. All mutations cluster to the last coding exon of the gene, suggesting that the mutant mRNA products escape nonsense-mediated decay and that the resulting truncated NOTCH2 proteins act in a gain-of-function manner.

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