par Denayer, Ellen;Devriendt, Koen;de Ravel, Thomy;Van Buggenhout, Griet;Smeets, Eric;François, Inge;Sznajer, Yves ;Craen, Margarita;Leventopoulos, George;Mutesa, Léon;Vandecasseye, Willy;Massa, Guy;Kayserili, Hulya;Sciot, Raf;Fryns, Jean-Pierre;Legius, Eric
Référence Genes chromosomes & cancer, 49, 3, page (242-252)
Publication Publié, 2010-03
Référence Genes chromosomes & cancer, 49, 3, page (242-252)
Publication Publié, 2010-03
Article révisé par les pairs
Résumé : | 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. © 2009 Wiley-Liss, Inc. |