title: [Phenotype variability in Noonan syndrome patients with and without PTPN11 mutation].
abstract: BACKGROUND
  Around 50% of Noonan syndrome (NS) patients present heterozygous mutations in the PTPN11 gene.
  
  
  OBJECTIVE
  To evaluate the frequency of mutations in the PTPN11 in patients with NS, and perform phenotype-genotype correlation.
  
  
  METHODS
  33 NS patients (23 males).
  
  
  METHODS
  DNA was extracted from peripheral blood leukocytes, and all 15 PTPN11 exons were directly sequenced.
  
  
  RESULTS
  Nine different missense mutations, including the novel P491H, were found in 16 of 33 NS patients. The most frequently observed features in NS patients were posteriorly rotated ears with thick helix (85%), short stature (79%), webbed neck (77%) and cryptorchidism (60%) in boys. The mean height SDS was -2.7 +/- 1.2 and BMI SDS was -1 +/- 1.4. Patients with PTPN11 mutations presented a higher incidence of pulmonary stenosis than patients without mutations (38% vs. 6%, p< 0.05). Patients with and without mutations did not present differences regarding height SDS, BMI SDS, frequency of thorax deformity, facial characteristics, cryptorchidism, mental retardation, learning disabilities, GH peak at stimulation test and IGF-1 or IGFBP-3 SDS.
  
  
  CONCLUSIONS
  We identified missense mutations in 48.5% of the NS patients. There was a positive correlation between the presence of PTPN11 mutations and pulmonary stenosis frequency in NS patients.
authors.affiliation: Laboratório de Hormônios e Genética Molecular, Disciplina de Endocrinologia do Departamento de Clínica Médica, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, SP, Brasil.
authors.forename: Lize V
authors.initials: LV
authors.lastname: Ferreira
authors.forename: Silvia A L
authors.initials: SA
authors.lastname: Souza
authors.forename: Luciana R
authors.initials: LR
authors.lastname: Montenegro
authors.forename: Ivo J P
authors.initials: IJ
authors.lastname: Arnhold
authors.forename: Titania
authors.initials: T
authors.lastname: Pasqualini
authors.forename: Juan Jorge
authors.initials: JJ
authors.lastname: Heinrich
authors.forename: Ana Claudia
authors.initials: AC
authors.lastname: Keselman
authors.forename: Berenice B
authors.initials: BB
authors.lastname: Mendonça
authors.forename: Alexander A L
authors.initials: AA
authors.lastname: Jorge
mesh_terms: D000293:Adolescent; D001827:Body Height / Q000187:drug effects; D002648:Child; D005260:Female; D005838:Genotype; D006130:Growth Disorders / Q000188:drug therapy / Q000209:etiology*; D019382:Human Growth Hormone / Q000627:therapeutic use; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D009634:Noonan Syndrome / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D010641:Phenotype; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics*
chemical_list: D019382:Human Growth Hormone; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11