Introduction: Around 50% of Noonan syndrome (NS) patients present heterozygous mutations in the PTPN11 gene.
Aim: To evaluate the frequency of mutations in the PTPN11 in patients with NS, and perform phenotype-genotype correlation.
Patients: 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.
Conclusion: 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.