A restricted spectrum of NRAS mutations causes Noonan syndrome.
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.
Cirstea
Ion C
IC
Institute of Biochemistry and Molecular Biology II, Heinrich-Heine University Medical Center, Düsseldorf, Germany.
Kutsche
Kerstin
K
Dvorsky
Radovan
R
Gremer
Lothar
L
Carta
Claudio
C
Horn
Denise
D
Roberts
Amy E
AE
Lepri
Francesca
F
Merbitz-Zahradnik
Torsten
T
König
Rainer
R
Kratz
Christian P
CP
Pantaleoni
Francesca
F
Dentici
Maria L
ML
Joshi
Victoria A
VA
Kucherlapati
Raju S
RS
Mazzanti
Laura
L
Mundlos
Stefan
S
Patton
Michael A
MA
Silengo
Margherita Cirillo
MC
Rossi
Cesare
C
Zampino
Giuseppe
G
Digilio
Cristina
C
Stuppia
Liborio
L
Seemanova
Eva
E
Pennacchio
Len A
LA
Gelb
Bruce D
BD
Dallapiccola
Bruno
B
Wittinghofer
Alfred
A
Ahmadian
Mohammad R
MR
Tartaglia
Marco
M
Zenker
Martin
M
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*
D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins