6533b7cffe1ef96bd1258f7c
RESEARCH PRODUCT
Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis.
Dominique Martin-coignardMartine Le MerrerMartine Le MerrerMartine Le MerrerBertrand IsidorChristian DinaChristian DinaChristian DinaAlbert DavidPierre LindenbaumPierre LindenbaumChristel Thauvin-robinetValérie Cormier-daireValérie Cormier-daireValérie Cormier-daireOlivier PichonCédric Le CaignecJean-louis MandelStéphane BézieauRichard RedonRichard RedonLaurence FaivreSébastien Jacquemontsubject
AdultMaleHeterozygoteHajdu–Cheney syndromeAdolescentmedia_common.quotation_subjectNonsenseMolecular Sequence DataBiologymedicine.disease_causeHajdu-Cheney SyndromeFrameshift mutationExonYoung AdultRare DiseasesSkeletal disorderGeneticsmedicineHumansAmino Acid SequenceReceptor Notch2Frameshift MutationGeneExome sequencingmedia_commonGeneticsMutationBase SequenceDNAExonsMiddle Agedmedicine.diseasePedigreeCodon NonsenseChild PreschoolMutationFemaleSignal Transductiondescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2010-11-29 | Nature genetics |