title: Clinical and molecular characterization of 40 patients with Noonan syndrome.
abstract: Noonan syndrome (NS, OMIM 163950) is an autosomal dominant disorder, with a prevalence at birth of 1:1000-1:2500 live births, characterized by short stature, facial and skeletal dysmorphisms, cardiovascular defects and haematological anomalies. Missense mutations of PTPN11 gene account for approximately 50% of NS cases, while molecular lesions of other genes of the RAS/MAPK pathway -KRAS, SOS1 and RAF1 - play a minor role in the molecular pathogenesis of the disease. Forty patients were enrolled in the study with a PTPN11 mutation detection rate of 31.5%, including a novel missense mutation, Phe285Ile, in a familial case with high intrafamilial phenotypic variability. All patients negative for PTPN11 mutations were further screened for mutations of the KRAS, SOS1, and RAF1 genes, revealing a Thr266Lys substitution in SOS1 in a single patient, a newborn with a subtle phenotype, characterized by facial dysmorphisms and a mild pulmonic stenosis.
authors.affiliation: Department of Pediatrics, University of Torino, Torino, Italy. giovannibattista.ferrero@unito.it
authors.forename: Giovanni Battista
authors.initials: GB
authors.lastname: Ferrero
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Baldassarre
authors.forename: Angelo Giovanni
authors.initials: AG
authors.lastname: Delmonaco
authors.forename: Elisa
authors.initials: E
authors.lastname: Biamino
authors.forename: Elena
authors.initials: E
authors.lastname: Banaudi
authors.forename: Claudio
authors.initials: C
authors.lastname: Carta
authors.forename: Cesare
authors.initials: C
authors.lastname: Rossi
authors.forename: Margherita Cirillo
authors.initials: MC
authors.lastname: Silengo
mesh_terms: D006801:Humans; D020125:Mutation, Missense; D009634:Noonan Syndrome / Q000235:genetics* / Q000473:pathology; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics
chemical_list: C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11