We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis.
- Authors
Isidor, ,13Bertrand; Lindenbaum, Pierre; Pichon, Olivier; Bézieau, Stéphane; Dina, Christian; Jacquemont, Sébastien; Martin-Coignard, Dominique; Thauvin-Robinet, Christel; Le Merrer, Martine; Mandel, Jean-Louis; David, Albert; Faivre, Laurence; Cormier-Daire, Valérie; Redon, Richard; Le Caignec, Cédric
- 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.
- Subjects
GENETIC mutation; EXONS (Genetics); OSTEOPOROSIS; BONE resorption; MESSENGER RNA; PATIENTS
- Publication
Nature Genetics, 2011, Vol 43, Issue 4, p306
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.778