title: Analysis of the PTPN11 gene in idiopathic short stature children and Noonan syndrome patients.
abstract: BACKGROUND
  Mutations in the PTPN11 gene are the main cause of Noonan syndrome (NS). The presence of some NS features is a frequent finding in children with idiopathic short stature (ISS). These children can represent the milder end of the NS clinical spectrum and PTPN11 is a good candidate for involvement in the pathogenesis of ISS.
  
  
  OBJECTIVE
  To evaluate the presence of mutations in PTPN11 in ISS children who presented NS-related signs and in well-characterized NS patients.
  
  
  METHODS
  We studied 50 ISS children who presented at least two NS-associated signs but did not fulfil the criteria for NS diagnosis. Forty-nine NS patients diagnosed by the criteria of van der Burgt et al. were used to assess the adequacy of these criteria to select patients for PTPN11 mutation screening. The coding region of PTPN11 was amplified by polymerase chain reaction (PCR), followed by direct sequencing.
  
  
  RESULTS
  No mutations or polymorphisms were found in the coding region of the PTPN11 gene in ISS children. Nineteen of the 49 NS patients (39%) presented mutations in PTPN11. No single characteristic enabled us to distinguish between NS patients with or without PTPN11 mutations.
  
  
  CONCLUSIONS
  Considering that no mutations were found in the present cohort with NS-related signs, it is unlikely that mutations would be found in unselected ISS children. The van der Burgt et al. criteria are adequate in attaining NS diagnosis and selecting patients for molecular studies. Mutations in the PTPN11 gene are commonly involved in the pathogenesis of NS but are not a common cause of ISS.
authors.affiliation: Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular LIM/42, Disciplina de Endocrinologia da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil.
authors.forename: Lize V
authors.initials: LV
authors.lastname: Ferreira
authors.forename: Silvia C A L
authors.initials: SC
authors.lastname: Souza
authors.forename: Luciana R
authors.initials: LR
authors.lastname: Montenegro
authors.forename: Alexsandra C
authors.initials: AC
authors.lastname: Malaquias
authors.forename: Ivo J P
authors.initials: IJ
authors.lastname: Arnhold
authors.forename: Berenice B
authors.initials: BB
authors.lastname: Mendonca
authors.forename: Alexander A L
authors.initials: AA
authors.lastname: Jorge
mesh_terms: D000293:Adolescent; D001827:Body Height / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D006130:Growth Disorders / Q000150:complications / Q000235:genetics*; D006801:Humans; D008297:Male; D009634:Noonan Syndrome / Q000150:complications / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000032:analysis / Q000235:genetics*
chemical_list: C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11