title: Neurofibromatosis-Noonan syndrome: molecular evidence of the concurrence of both disorders in a patient.
abstract: Noonan syndrome (NS) is an autosomal dominant disorder characterized by short stature, facial anomalies, webbed neck, sternal deformity, heart defects, and, in males, cryptorchidism. PTPN11 encodes SHP2, an important component of several signal transduction pathways that acts as a positive regulator of RAS-mitogen activated protein kinase signaling. Neurofibromatosis type 1 (NF1) is another autosomal dominant disorder characterized by hamartomas in multiple organs. The NF1 gene encodes a GAP-related protein, which acts as a negative regulator of the Ras-mediated signal transduction pathway. Clinical overlap between both syndromes, neurofibromatosis-Noonan syndrome (NFNS) is well known. We studied a female patient with typical findings of NFNS and found two mutations: a novel PTPN11 transversion, 1909A --> G, resulting in Gln510Arg, and an NF1 transversion, 2531A --> G, resulting in Leu844Arg. She inherited the PTPN11 mutation from her father and had a de novo NF1 mutation. This is the first report of molecular concurrence of both disorders in the same patient.
authors.affiliation: Genetics Clinic Unit, Instituto da Criança do Hospital das Clínicas, University of São Paulo, São Paulo, Brazil. deborab@icr.hcnet.usp.br
authors.forename: Debora R
authors.initials: DR
authors.lastname: Bertola
authors.forename: Alexandre C
authors.initials: AC
authors.lastname: Pereira
authors.forename: Fábio
authors.initials: F
authors.lastname: Passetti
authors.forename: Paulo S L
authors.initials: PS
authors.lastname: de Oliveira
authors.forename: Ludwine
authors.initials: L
authors.lastname: Messiaen
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Gelb
authors.forename: Chong A
authors.initials: CA
authors.lastname: Kim
authors.forename: José Eduardo
authors.initials: JE
authors.lastname: Krieger
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D000293:Adolescent; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007621:Karyotyping; D020125:Mutation, Missense; D009456:Neurofibromatosis 1 / Q000473:pathology*; D025542:Neurofibromin 1 / Q000235:genetics*; D009634:Noonan Syndrome / Q000473:pathology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*
chemical_list: D025542:Neurofibromin 1; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases