Information from Genedx.
Germline mutations have been found in 59% of patients with familial Noonan syndrome and 37% of individuals with sporadic Noonan syndrome.
Genotype-phenotype correlation studies suggest that PTPN11 mutations were found with increased frequency in individuals with Noonan Syndrome and pulmonic stenosis (70%), while those with hypertrophic cardiomyopathy were infrequently found to have PTPN11 mutations (6%) (Tartaglia, 2002).
Using genomic DNA obtained from buccal swabs, exons 3 and 8 of the PTPN11 gene are screened by bi-directional sequence analysis in the first tier of the analysis.
If no mutation is found, the remaining PTPN11 exons will be sequenced upon request. Using this two-tiered approach, we expect to identify three-fourths of PTPN11 mutations in the first testing tier, thereby keeping the cost down for the majority of patients.
Using our testing approach, 77% of published mutations would be detected in the first tier analysis.
The remaining 23% of reported mutations would be identified by sequencing the remaining 13 exons of the gene.
Taking into consideration the genetic heterogeneity of Noonan Syndrome and an overall PTPN11 mutation rate of 50% (familial and sporadic cases), first tier testing has a sensitivity of 35%, while testing the remaining exons increases sensitivity to about 50%.
Prenatal diagnosis is available once the mutation in a family has been defined.