title: Tumor spectrum in children with Noonan syndrome and SOS1 or RAF1 mutations.
abstract: Noonan syndrome (NS) is an autosomal dominant disorder caused by mutations in PTPN11, KRAS, SOS1, and RAF1. We performed SOS1, RAF1, BRAF, MEK1, and MEK2 mutation analysis in a cohort of 102 PTPN11- and KRAS-negative NS patients and found pathogenic SOS1 mutations in 10, RAF1 mutations in 4, and BRAF mutations in 2 patients. Three novel SOS1 mutations were found. One was classified as a rare benign variant and the other remains unclassified. We confirm a high prevalence of pulmonic stenosis and ectodermal abnormalities in SOS1-positive patients. Three patients with SOS1 mutations presented with tumors (embryonal rhabdomyosarcoma, Sertoli cell testis tumor, and granular cell tumors of the skin). One patient with a RAF1 mutation had a lesion suggestive for a giant cell tumor. This is the first report describing different tumor types in NS patients with germ line SOS1 mutations.
authors: Department of Human Genetics, University of Leuven, Leuven, Belgium.
authors: Ellen
authors: E
authors: Denayer
authors: Koen
authors: K
authors: Devriendt
authors: Thomy
authors: T
authors: de Ravel
authors: Griet
authors: G
authors: Van Buggenhout
authors: Eric
authors: E
authors: Smeets
authors: Inge
authors: I
authors: Francois
authors: Yves
authors: Y
authors: Sznajer
authors: Margarita
authors: M
authors: Craen
authors: George
authors: G
authors: Leventopoulos
authors: Léon
authors: L
authors: Mutesa
authors: Willy
authors: W
authors: Vandecasseye
authors: Guy
authors: G
authors: Massa
authors: Hulya
authors: H
authors: Kayserili
authors: Raf
authors: R
authors: Sciot
authors: Jean-Pierre
authors: JP
authors: Fryns
authors: Eric
authors: E
authors: Legius
mesh_terms: D000293:Adolescent; D019943:Amino Acid Substitution; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons; D020440:Gene Duplication; D006801:Humans; D007962:Leukocytes / Q000502:physiology; D048369:MAP Kinase Kinase 1 / Q000235:genetics; D048370:MAP Kinase Kinase 2 / Q000235:genetics; D009154:Mutation; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics*; D009634:Noonan Syndrome / Q000150:complications / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics*; D020837:SOS1 Protein / Q000235:genetics*; D055815:Young Adult
chemical_list: D020837:SOS1 Protein; C482128:MAP2K2 protein, human; D019908:Proto-Oncogene Proteins c-raf; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482125:MAP2K1 protein, human