High resolution melting analysis for mutation detection for PTPN11 gene: Applications of this method for diagnosis of Noonan syndrome

Background: Noonan syndrome (NS, OMIM 163950) is a relatively common autosomal dominant disorder and has significant phenotypic overlap with Costello Syndrome and cardio-facio-cutaneous syndrome. Molecular diagnosis is useful for differential diagnosis. PTPN11 gene mutation is the most common mutation associated with NS and hence is a suitable target for molecular diagnostics. Methods: High resolution melting (HRM) analysis was used for screening of PTPN11 mutations. Eleven DNA samples with 10 known PTPN11 mutations were used for HRM calibration. Said calibrations were then applied to mutation screening of a panel of 50 additional NS patients. Results: HRM analysis differentiated all of the 10 known mutations and identified 9 additional mutations from 10 patients in the blind study, which is in line with results obtained by sequencing. Conclusions: HRM analysis is a rapid, reliable, and low-cost tool for detection of PTPN11 genetic variants.