title: PTPN11 and KRAS gene analysis in patients with Noonan and Noonan-like syndromes.
abstract: Noonan and Noonan-like syndromes are disorders of dysregulation of the rat sarcoma viral oncogene homolog (RAS)-mitogen-activated protein kinase signaling pathway. In Noonan syndrome (NS), four genes of this pathway (PTPN11, SOS1, RAF1, and KRAS) are responsible for roughly 70% of the cases. We analyzed PTPN11 and KRAS genes by bidirectional sequencing in 95 probands with NS and 29 with Noonan-like syndromes, including previously reported patients already screened for PTPN11 gene mutations. In the new patients with NS, 20/46 (43%) showed a PTPN11 gene mutation, two of them novel. In our total cohort, patients with NS and a PTPN11 mutation presented significantly higher prevalence of short stature (p = 0.03) and pulmonary valve stenosis (p = 0.01), and lower prevalence of hypertrophic cardiomyopathy (p = 0.01). Only a single gene alteration, of uncertain role, was found in the KRAS gene in an NS patient also presenting a PTPN11 gene mutation. We further analyzed the influence in clinical variability of three frequent polymorphisms found in the KRAS gene and no statistically significant difference was observed among the frequency of clinical findings regarding the studied polymorphisms.
authors.affiliation: Unidade de Genética, Instituto da Criança, São Paulo, Brazil.
authors.forename: Amanda Salem
authors.initials: AS
authors.lastname: Brasil
authors.forename: Alexandre C
authors.initials: AC
authors.lastname: Pereira
authors.forename: Luciana Turolla
authors.initials: LT
authors.lastname: Wanderley
authors.forename: Chong Ae
authors.initials: CA
authors.lastname: Kim
authors.forename: Alexsandra C
authors.initials: AC
authors.lastname: Malaquias
authors.forename: Alexander A L
authors.initials: AA
authors.lastname: Jorge
authors.forename: José Eduardo
authors.initials: JE
authors.lastname: Krieger
authors.forename: Débora Romeo
authors.initials: DR
authors.lastname: Bertola
mesh_terms: D000293:Adolescent; D000328:Adult; D002312:Cardiomyopathy, Hypertrophic; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D009634:Noonan Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D010641:Phenotype; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D011666:Pulmonary Valve Stenosis; D013577:Syndrome; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins