A restricted spectrum of NRAS mutations causes Noonan syndrome

Ion C. Cirstea; Kerstin Kutsche; Radovan Dvorsky; Lothar Gremer; Claudio Carta; Denise Horn; Amy E. Roberts; Francesca Lepri; Torsten Merbitz-Zahradnik; Rainer König; Christian P. Kratz; Francesca Pantaleoni; Maria L. Dentici; Victoria A. Joshi; Raju S. Kucherlapati; Laura Mazzanti; Stefan Mundlos; Michael A. Patton; Margherita Cirillo Silengo; Cesare Rossi; Giuseppe Zampino; Cristina Digilio; Liborio Stuppia; Eva Seemanova; Len A. Pennacchio; Bruce D. Gelb; Bruno Dallapiccola; Alfred Wittinghofer; Mohammad R. Ahmadian; Marco Tartaglia; Martin Zenker

doi:10.1038/ng.497

A restricted spectrum of NRAS mutations causes Noonan syndrome

Ion C. Cirstea, Kerstin Kutsche, Radovan Dvorsky, Lothar Gremer, Claudio Carta, Denise Horn, Amy E. Roberts, Francesca Lepri, Torsten Merbitz-Zahradnik, Rainer König, Christian P. Kratz, Francesca Pantaleoni, Maria L. Dentici, Victoria A. Joshi, Raju S. Kucherlapati, Laura Mazzanti, Stefan Mundlos, Michael A. Patton, Margherita Cirillo Silengo, Cesare RossiGiuseppe Zampino, Cristina Digilio, Liborio Stuppia, Eva Seemanova, Len A. Pennacchio, Bruce D. Gelb, Bruno Dallapiccola, Alfred Wittinghofer, Mohammad R. Ahmadian, Marco Tartaglia, Martin Zenker

Ospedale Pediatrico Bambino Gesu

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	27-29
Number of pages	3
Journal	Nature Genetics
Volume	42
Issue number	1
DOIs	https://doi.org/10.1038/ng.497
Publication status	Published - Jan 2010

ASJC Scopus subject areas

Genetics

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Cirstea, I. C., Kutsche, K., Dvorsky, R., Gremer, L., Carta, C., Horn, D., Roberts, A. E., Lepri, F., Merbitz-Zahradnik, T., König, R., Kratz, C. P., Pantaleoni, F., Dentici, M. L., Joshi, V. A., Kucherlapati, R. S., Mazzanti, L., Mundlos, S., Patton, M. A., Silengo, M. C., ... Zenker, M. (2010). A restricted spectrum of NRAS mutations causes Noonan syndrome. Nature Genetics, 42(1), 27-29. https://doi.org/10.1038/ng.497

Cirstea, IC, Kutsche, K, Dvorsky, R, Gremer, L, Carta, C, Horn, D, Roberts, AE, Lepri, F, Merbitz-Zahradnik, T, König, R, Kratz, CP, Pantaleoni, F, Dentici, ML, Joshi, VA, Kucherlapati, RS, Mazzanti, L, Mundlos, S, Patton, MA, Silengo, MC, Rossi, C, Zampino, G, Digilio, C, Stuppia, L, Seemanova, E, Pennacchio, LA, Gelb, BD, Dallapiccola, B, Wittinghofer, A, Ahmadian, MR, Tartaglia, M & Zenker, M 2010, 'A restricted spectrum of NRAS mutations causes Noonan syndrome', Nature Genetics, vol. 42, no. 1, pp. 27-29. https://doi.org/10.1038/ng.497

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title = "A restricted spectrum of NRAS mutations causes Noonan syndrome",

abstract = "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.",

author = "Cirstea, {Ion C.} and Kerstin Kutsche and Radovan Dvorsky and Lothar Gremer and Claudio Carta and Denise Horn and Roberts, {Amy E.} and Francesca Lepri and Torsten Merbitz-Zahradnik and Rainer K{\"o}nig and Kratz, {Christian P.} and Francesca Pantaleoni and Dentici, {Maria L.} and Joshi, {Victoria A.} and Kucherlapati, {Raju S.} and Laura Mazzanti and Stefan Mundlos and Patton, {Michael A.} and Silengo, {Margherita Cirillo} and Cesare Rossi and Giuseppe Zampino and Cristina Digilio and Liborio Stuppia and Eva Seemanova and Pennacchio, {Len A.} and Gelb, {Bruce D.} and Bruno Dallapiccola and Alfred Wittinghofer and Ahmadian, {Mohammad R.} and Marco Tartaglia and Martin Zenker",

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AU - Dvorsky, Radovan

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AU - Carta, Claudio

AU - Horn, Denise

AU - Roberts, Amy E.

AU - Lepri, Francesca

AU - Merbitz-Zahradnik, Torsten

AU - König, Rainer

AU - Kratz, Christian P.

AU - Pantaleoni, Francesca

AU - Dentici, Maria L.

AU - Joshi, Victoria A.

AU - Kucherlapati, Raju S.

AU - Mazzanti, Laura

AU - Mundlos, Stefan

AU - Patton, Michael A.

AU - Silengo, Margherita Cirillo

AU - Rossi, Cesare

AU - Zampino, Giuseppe

AU - Digilio, Cristina

AU - Stuppia, Liborio

AU - Seemanova, Eva

AU - Pennacchio, Len A.

AU - Gelb, Bruce D.

AU - Dallapiccola, Bruno

AU - Wittinghofer, Alfred

AU - Ahmadian, Mohammad R.

AU - Tartaglia, Marco

AU - Zenker, Martin

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A restricted spectrum of NRAS mutations causes Noonan syndrome

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