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PTPN11 and KRAS gene analysis in patients with Noonan and Noonan-like syndromes

Amanda Salem Brasil1, Alexandre C Pereira, Luciana Turolla Wanderley

  • 1Unidade de Genética, Instituto da Criança, São Paulo, Brazil.

Genetic Testing and Molecular Biomarkers
|June 29, 2010
PubMed

Insights

Noonan syndrome (NS) is linked to the RAS-MAPK pathway. PTPN11 gene mutations are common in NS, correlating with short stature and pulmonary valve stenosis, but not hypertrophic cardiomyopathy.

Area of Science:

  • Genetics
  • Molecular Biology
  • Clinical Medicine

Background:

  • Noonan syndrome (NS) and Noonan-like syndromes involve dysregulation of the RAS-MAPK signaling pathway.
  • Key genes implicated include PTPN11, SOS1, RAF1, and KRAS, accounting for approximately 70% of NS cases.

Purpose of the Study:

  • To investigate the prevalence and clinical impact of PTPN11 and KRAS gene mutations in patients with Noonan syndrome and Noonan-like syndromes.
  • To analyze the association between PTPN11 mutations and specific clinical phenotypes in NS.

Main Methods:

  • Bidirectional sequencing of PTPN11 and KRAS genes was performed on 95 NS probands and 29 with Noonan-like syndromes.
  • Analysis included previously reported patients screened for PTPN11 mutations.
  • Clinical data was correlated with identified genetic alterations and KRAS polymorphisms.

Main Results:

  • Novel PTPN11 mutations were identified in 43% of new NS patients (2/46).
  • In the total cohort, PTPN11 mutations in NS patients were significantly associated with increased short stature (p=0.03) and pulmonary valve stenosis (p=0.01).
  • A decreased prevalence of hypertrophic cardiomyopathy (p=0.01) was observed in NS patients with PTPN11 mutations. KRAS gene alterations showed uncertain roles, and KRAS polymorphisms did not significantly influence clinical findings.

Conclusions:

  • PTPN11 gene mutations are a significant factor in Noonan syndrome pathogenesis and clinical presentation.
  • Specific PTPN11 mutations correlate with distinct clinical features, aiding in phenotype-genotype understanding.
  • Further research into KRAS gene variants may be warranted, but current evidence suggests limited impact on NS clinical variability.

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