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

被引：141

作者：

Isidor, Bertrand ^{[1
]}

Lindenbaum, Pierre ^{[1
,2
,3
]}

Pichon, Olivier ^{[1
]}

Bezieau, Stephane ^{[1
,3
]}

Dina, Christian ^{[2
,3
,4
]}

Jacquemont, Sebastien ^{[5
]}

Martin-Coignard, Dominique ^{[6
]}

Thauvin-Robinet, Christel ^{[7
,8
]}

Le Merrer, Martine ^{[9
,10
,11
]}

Mandel, Jean-Louis ^{[12
,13
,14
,15
,16
]}

David, Albert ^{[1
]}

Faivre, Laurence ^{[7
,8
]}

Cormier-Daire, Valerie ^{[9
,10
,11
]}

Redon, Richard ^{[1
,2
,3
]}

Le Caignec, Cedric ^{[1
,2
,3
,4
]}

机构：

[1] CHU Nantes, Serv Genet Med, F-44035 Nantes 01, France

[2] INSERM, Inst Thorax, UMR915, Nantes, France

[3] Univ Nantes, Nantes, France

[4] CNRS, ERL3147, Nantes, France

[5] CHUV, Serv Genet Med, Lausanne, Switzerland

[6] Ctr Hosp Mans, Unit Genet Clin, Le Mans, France

[7] CHU, Ctr Genet, Ctr Reference Malad Rares Anomalies Dev & Syndrom, Est Hop Enfants, Dijon, France

[8] Univ Bourgogne, Dijon, France

[9] INSERM, U781, Paris, France

[10] Hop Necker Enfants Malad, Dept Genet, Paris, France

[11] Univ Paris 05, Paris, France

[12] Coll France, IGBMC, Translat Med & Neurogenet Program, Illkirch Graffenstaden, France

[13] INSERM, U964, Illkirch Graffenstaden, France

[14] CNRS, UMR 7104, Illkirch Graffenstaden, France

[15] Univ Strasbourg, Illkirch Graffenstaden, France

[16] CHU Strasbourg, F-67000 Strasbourg, France

来源：

NATURE GENETICS | 2011年 / 43卷 / 04期

关键词：

ALAGILLE-SYNDROME; OSTEOBLAST DIFFERENTIATION; SIGNALING PATHWAY;

D O I：

10.1038/ng.778

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：306 / 308

页数：3

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