Biologia e Medicina

Abstrato

Further Evidence for the Implication of LZTR1, a Gene not Associated with the Ras-Mapk Pathway, in the Pathogenesis of Noonan Syndrome

Nehla Ghedira, Lilia Kraoua, Arnaud Lagarde, Rim Ben Abdelaziz, Sylviane Olschwang, Jean Pierre Desvignes, Sonia Abdelhak, Kamel Monastiri, Nicolas Levy, Annachiara De Sandre-Giovannoli and Ridha Mrad

Background: Noonan Syndrome (NS) is a relatively common autosomal dominant condition, caused by germline mutations in different genes involved in the RAS MAP Kinase signaling pathway. Although clinically heterogeneous, characteristic findings include typical facial features, short stature, chest deformity and congenital heart diseases.

Methods: Here, we present the clinical and molecular characterization of a Tunisian patient with NS. A comprehensive mutations analysis of 29 genes belonging to the RAS pathway or encoding for interactors was performed, using targeted next generation sequencing.

Results: The results revealed a novel pathogenic substitution affecting the LZTR1, whose mutations have been described only in 5 cases of NS.

Conclusion: This report supports the implication of LZTR1 in Noonan syndrome. Next Generation Sequencing seems a suitable method for mutation detection in clinically and genetically heterogeneous syndromes such as NS.