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

Date publication

janvier 2011

Auteurs

Membres identifiés du Cancéropôle Est :
Pr MANDEL Jean-Louis

Tous les auteurs :
Isidor B, Lindenbaum P, Pichon O, Bezieau S, Dina C, Jacquemont S, Martin-Coignard D, Thauvin-Robinet C, Le Merrer M, Mandel JL, David A, Faivre L, Cormier-Daire V, Redon R, Le Caignec C

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/21378989

Résumé

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.

Référence

Nat Genet. 2011 Mar 6;43(4):306-8.