High Prevalence Noonan Syndrome In Russian Children With Hypertrophic Cardiomyopathy, Diagnosed By Next Generation Sequencing

Backgraund Noonan syndrome - is rare autosomal dominant disorder from RASopathies group, characterized by facial dysmorphism, short stature, hypertrophic cardiomyopathy, congenital heart defects. Patients and Methods We have examined 47 patients with hypertrophic cardiomyopathy aged 1 to 17 years. Target areas of the exome were investigated by NGS. Bioinformatic analysis was carried out using the Alamut software. Validation of the identified variants was carried out by the Sanger method. Results The diagnosis was confirmed in 13 patients with hypertrophic cardiomyopathy and cardiologic abnormalities. Short stature and facial features have all our patients. Congenital heart defect, including pulmonic stenosis diagnosed in 6 cases. RAF1 mutations were identified in 7 patients, PTPN11 - in 3 patients, SOS1- in 1 patient, SOS 2 - in 1 patient, and RIT1 - in 1 patient. Most frequent RAF1 mutation was c.770C>T, p. S257L (5 from 7 cases). Girl with mutation in RIT-1 was with phenotype Noonan syndrome, but she also have left ventricular noncompaction and skin cafe-au-lait spots. Conclusion Noonan syndrome was diagnosed in 28% hypertrophic cardiomyopathy patients. Mutation c.770C>T, p.S257L in RAF1 gen is most common in hypertrophic cardiomyopathy patients with Noonan syndrome