title: Co-occurring PTPN11 and SOS1 gene mutations in Noonan syndrome: does this predict a more severe phenotype?
abstract: Noonan syndrome (NS) is an autosomal dominant disorder, with variable phenotypic expression, characterized by short stature, facial dysmorphisms and heart disease. Different genes of the RAS/MAPK signaling pathway are responsible for the syndrome, the most common are: PTPN11, SOS1, RAF1, and KRAS. The objective of this study was to report a patient with Noonan syndrome presenting mutations in two genes of RAS/MAPK pathway in order to establish whether these mutations lead to a more severe expression of the phenotype. We used direct sequencing of the PTPN11, SOS1, RAF1, and KRAS genes. We have identified two described mutations in heterozygosity: p.N308D and p.R552G in the genes PTPN11 and SOS1, respectively. The patient has typical clinical features similar to the ones with NS and mutation in only one gene, even those with the same mutation identified in this patient. A more severe or atypical phenotype was not observed, suggesting that these mutations do not exhibit an additive effect.
authors.affiliation: Genetics Unit, Children’s Institute, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil. amandasb@usp.br
authors.forename: Amanda Salem
authors.initials: AS
authors.lastname: Brasil
authors.forename: Alexsandra C
authors.initials: AC
authors.lastname: Malaquias
authors.forename: Luciana Turolla
authors.initials: LT
authors.lastname: Wanderley
authors.forename: Chong Ae
authors.initials: CA
authors.lastname: Kim
authors.forename: José Eduardo
authors.initials: JE
authors.lastname: Krieger
authors.forename: Alexander A L
authors.initials: AA
authors.lastname: Jorge
authors.forename: Alexandre C
authors.initials: AC
authors.lastname: Pereira
authors.forename: Débora Romeo
authors.initials: DR
authors.lastname: Bertola
mesh_terms: D002648:Child; D005260:Female; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D009634:Noonan Syndrome / Q000235:genetics*; D010641:Phenotype; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics*; D020837:SOS1 Protein / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D020837:SOS1 Protein; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11