title: [RIT1: a novel gene associated with Noonan syndrome].
abstract: BACKGROUND
  Noonan syndrome is the most frequent of the congenital group of malformation syndromes caused by germline mutations that encode components of the RAS/MAPK pathway, termed RASopathies, one of the most frequent congenital genetic disorders in the clinical practice. Recently RIT1 mutations have been reported in patients with Noonan syndrome.
  
  
  METHODS
  A 7 years-old girl with a clinical diagnosis of Noonan syndrome, and with a hypertrophic cardiomyopathy included in her clinical manifestations, where a de novo heterozygous, probably pathogenic, novel mutation in RIT1, c.295T>C (p.Phe99Leu), has been identified.
  
  
  CONCLUSIONS
  RIT1 shares homology with other RAS proteins and the expression of mutant alleles demonstrates a gain-of-function effect supporting a causative role in Noonan syndrome pathogenesis. Data suggest that the frequency of RIT1 mutations can be estimated as 3-5% in Noonan syndrome patients. These cases compared with Noonan patients harboring mutations in other genes are characterized by high frequency of prenatal abnormalities and hypertrophic cardiomyopathy, and lower frequencies of short stature and pectus abnormalities. We emphasize the importance of the novel identified genes in order to be included in the diagnostic panels.
authors.affiliation: Hospital San Pedro de Alcantara, 10003 Caceres, Espana.|Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER). ISCIII, Madrid, Espana.
authors.forename: I
authors.initials: I
authors.lastname: Arroyo-Carrera
authors.affiliation: Hospital San Pedro de Alcantara, 10003 Caceres, Espana.
authors.forename: M
authors.initials: M
authors.lastname: Solo de Zaldivar-Tristancho
authors.affiliation: Hospital San Pedro de Alcantara, 10003 Caceres, Espana.
authors.forename: R
authors.initials: R
authors.lastname: Martin-Fernandez
authors.affiliation: Hospital San Pedro de Alcantara, 10003 Caceres, Espana.
authors.forename: M
authors.initials: M
authors.lastname: Vera-Torres
authors.affiliation: Hospital San Pedro de Alcantara, 10003 Caceres, Espana.
authors.forename: J F
authors.initials: JF
authors.lastname: Gonzalez de Buitrago-Amigo
authors.affiliation: NIMGENETICS (New Integrated Medical Genetics). Parque Cientifico de Madrid, Madrid, Espana.
authors.forename: J
authors.initials: J
authors.lastname: Botet-Rodriguez
mesh_terms: D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D002648:Child; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D009634:Noonan Syndrome / Q000235:genetics*; D018631:ras Proteins / Q000235:genetics*
chemical_list: C486776:RIT1 protein, human; D018631:ras Proteins