Analysis of the lipids and carbohydrates metabolisms in Noonan syndrome patients

Abstract

Noonan syndrome (NS) is an autosomal dominant disease characterized by postnatal short stature, facial dimorphisms, congenital heart disease and thoracic deformity. Germline mutations found in components of the RAS/MAPK signaling pathway have been described in patients with NS and other rare syndromes whose phenotype overlaps the SN, explaining the molecular cause in about 75 % of cases. The RAS/MAPK signaling pathway translates the signal generated by growth factors to the nucleus and participates in various biological functions such as cell growth, survival and differentiation. Other hormones, such as insulin and leptin, also use components of RAS/MAPK signaling pathway for signal transduction and transcription of proteins important in the lipids and carbohydrates metabolisms. However, the role of the RAS/MAPK pathway in the metabolic profile of patients with NS remains unclear. So, it is of great interest to characterize the influence of the constitutive activation of the RAS / MAPK pathway in the lipids and carbohydrates metabolisms of these patients. The goal of this project is to determine the correlation between genotype and phenotype in Noonan syndrome with emphasis on carbohydrate and lipid variables and evaluate the energy balance of patients with NS and Noonan-like syndromes, correlating with the anthropometric parameters such as weight and body mass index. Moreover, fibroblasts in a group of patients with NS will be studied to evaluate insulin signaling through RAS/MAPK and PI3K/AKT pathways. The role of NS mutations in the carbohydrates and lipids metabolisms is very important for the recognition of new therapeutic targets for the treatment of Noonan syndrome. (AU)