PTPN11, SOS1, KRAS, and RAF1 gene analysis, and genotype –phenotype correlation in Korean patients with Noonan syndrome

AbstractAfter 2006, germline mutations in theKRAS,SOS1, andRAF1 genes were reported to cause Noonan syndrome (NS), in addition to thePTPN11 gene, and now we can find the etiology of disease in approximately 60 –70% of NS cases. The aim of this study was to assess the correlation between phenotype and genotype by molecular analysis of thePTPN11,SOS1,KRAS, andRAF1 genes in 59 Korean patients with NS. We found disease-causing mutations in 30 (50.8%) patients, which were located in thePTPN11 (27.1%),SOS1 (16.9%),KRAS (1.7%), andRAF1 (5.1%) genes. Three novel mutations (T59A inPTPN11, K170E inSOS1, S259T inRAF1) were identified. The patients withPTPN11 mutations showed higher prevalences of patent ductus arteriosus and thrombocytopenia. The patients withSOS1 mutations had a lower prevalence of delayed psychomotor development. All patients withRAF1 mutations had hypertrophic cardiomyopathy. Typical facial features and auxological parameters were, on statistical analysis, not significantly different between the groups. The molecular defects of NS are genetically heterogeneous and involve several genes other thanPTPN11 related to the RAS-MAPK pathway.
Source: Journal of Human Genetics - Category: Genetics & Stem Cells Source Type: research