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.
authors: Institute of Biochemistry and Molecular Biology II, Heinrich-Heine University Medical Center, Düsseldorf, Germany.
authors: Ion C
authors: IC
authors: Cirstea
authors: Kerstin
authors: K
authors: Kutsche
authors: Radovan
authors: R
authors: Dvorsky
authors: Lothar
authors: L
authors: Gremer
authors: Claudio
authors: C
authors: Carta
authors: Denise
authors: D
authors: Horn
authors: Amy E
authors: AE
authors: Roberts
authors: Francesca
authors: F
authors: Lepri
authors: Torsten
authors: T
authors: Merbitz-Zahradnik
authors: Rainer
authors: R
authors: König
authors: Christian P
authors: CP
authors: Kratz
authors: Francesca
authors: F
authors: Pantaleoni
authors: Maria L
authors: ML
authors: Dentici
authors: Victoria A
authors: VA
authors: Joshi
authors: Raju S
authors: RS
authors: Kucherlapati
authors: Laura
authors: L
authors: Mazzanti
authors: Stefan
authors: S
authors: Mundlos
authors: Michael A
authors: MA
authors: Patton
authors: Margherita Cirillo
authors: MC
authors: Silengo
authors: Cesare
authors: C
authors: Rossi
authors: Giuseppe
authors: G
authors: Zampino
authors: Cristina
authors: C
authors: Digilio
authors: Liborio
authors: L
authors: Stuppia
authors: Eva
authors: E
authors: Seemanova
authors: Len A
authors: LA
authors: Pennacchio
authors: Bruce D
authors: BD
authors: Gelb
authors: Bruno
authors: B
authors: Dallapiccola
authors: Alfred
authors: A
authors: Wittinghofer
authors: Mohammad R
authors: MR
authors: Ahmadian
authors: Marco
authors: M
authors: Tartaglia
authors: Martin
authors: M
authors: Zenker
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002648:Child; D002675:Child, Preschool; D002522:Chlorocebus aethiops; D004252:DNA Mutational Analysis; D005260:Female; D011905:Genes, ras; D006801:Humans; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009634:Noonan Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D055815:Young Adult; D018631:ras Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins