A restricted spectrum of NRAS mutations causes Noonan syndrome

被引：227

作者：

Cirstea, Ion C. ^{[2
]}

Kutsche, Kerstin ^{[3
]}

Dvorsky, Radovan ^{[2
]}

Gremer, Lothar ^{[2
]}

Carta, Claudio ^{[4
]}

Horn, Denise ^{[5
]}

Roberts, Amy E. ^{[6
,7
]}

Lepri, Francesca ^{[8
,9
]}

Merbitz-Zahradnik, Torsten ^{[2
]}

Koenig, Rainer ^{[10
]}

Kratz, Christian P. ^{[11
,12
]}

Pantaleoni, Francesca ^{[4
]}

Dentici, Maria L. ^{[8
,9
]}

Joshi, Victoria A. ^{[6
,13
,14
]}

Kucherlapati, Raju S. ^{[6
]}

Mazzanti, Laura ^{[15
]}

Mundlos, Stefan ^{[5
]}

Patton, Michael A. ^{[16
]}

Silengo, Margherita Cirillo ^{[17
]}

Rossi, Cesare ^{[18
]}

Zampino, Giuseppe ^{[19
]}

Digilio, Cristina ^{[20
]}

Stuppia, Liborio ^{[21
]}

Seemanova, Eva ^{[22
]}

Pennacchio, Len A. ^{[23
,24
]}

Gelb, Bruce D. ^{[25
,26
,27
]}

Dallapiccola, Bruno ^{[8
,9
]}

Wittinghofer, Alfred ^{[1
]}

Ahmadian, Mohammad R. ^{[2
]}

Tartaglia, Marco ^{[4
]}

Zenker, Martin ^{[1
,28
,29
]}

机构：

[1] Max Planck Inst Mol Physiol, Dept Biol Struct, D-44139 Dortmund, Germany

[2] Univ Dusseldorf, Med Ctr, Inst Biochem & Mol Biol 2, Dusseldorf, Germany

[3] Univ Klinikum Hamburg Eppendorf, Inst Humangenet, Hamburg, Germany

[4] Ist Super Sanita, Dipartimento Ematol Oncol & Med Mol, I-00161 Rome, Italy

[5] Charite, Inst Med Genet, D-13353 Berlin, Germany

[6] Harvard Univ, Sch Med, Boston, MA USA

[7] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA

[8] Ist Ricovero & Cura Carattere Sci Casa Sollievo S, San Giovanni Rotondo, Italy

[9] Casa Sollievo Sofferenza Ist Mendel, Rome, Italy

[10] Goethe Univ Frankfurt, Inst Human Genet, Frankfurt, Germany

[11] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA

[12] Univ Freiburg, Dept Paediat & Adolescent Med, Freiburg, Germany

[13] Partners HealthCare Ctr Personalized Genet Med, Boston, MA USA

[14] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

[15] Univ Bologna, Dipartimento Pediat, Bologna, Italy

[16] Univ London St Georges Hosp, Dept Clin Genet, London, England

[17] Univ Turin, Dipartimento Pediat, Turin, Italy

[18] St Orsola Marcello Malpighi Hosp, Unita Operat Genet Med, Bologna, Italy

[19] Univ Cattolica Sacro Cuore, Ist Clin Pediat, Rome, Italy

[20] Bambino Gesu Pediat Hosp, Sez Genet Med, Rome, Italy

[21] Univ G DAnnunzio, Dipartimento Sci Biomed, Chieti, Italy

[22] Charles Univ Prague, Univ Hosp Prague, Inst Biol & Med Genet, Prague, Czech Republic

[23] Univ Calif Berkeley, Lawrence Berkeley Lab, Genom Div, Berkeley, CA 94720 USA

[24] US DOE, Joint Genome Inst, Walnut Creek, CA USA

[25] Mt Sinai Sch Med, Ctr Mol Cardiol, New York, NY USA

[26] Mt Sinai Sch Med, Dept Pediat, New York, NY USA

[27] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA

[28] Univ Erlangen Nurnberg, Inst Human Genet, Univ Hosp Erlangen, D-8520 Erlangen, Germany

[29] Otto Von Guericke Univ, Univ Hosp Magdeburg, Inst Human Genet, Magdeburg, Germany

来源：

NATURE GENETICS | 2010年 / 42卷 / 01期

关键词：

RAS PROTEINS; DISORDERS; CANCER; SWITCH; KRAS;

D O I：

10.1038/ng.497

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Noonan syndrome, a developmental disorder characterized by congenital heart defects, reduced growth, facial dysmorphism and variable cognitive deficits, is caused by constitutional dysregulation of the RAS-MAPK signaling pathway. Here we report that germline NRAS mutations conferring enhanced stimulus-dependent MAPK activation account for some cases of this disorder. These findings provide evidence for an obligate dependency on proper NRAS function in human development and growth.

引用

页码：27 / 29

页数：3

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