生物学と医学

概要

Further evidence implicating LZTR1, a gene not associated with the Ras-Mapk pathway, in the pathogenesis of Noonan syndrome.

Neela Ghedira, Lilia Klauer, Arnaud Lagarde, Rim Ben Abdelaziz, Sylvian Olschwang, Jean-Pierre Devigne, Sonia Abdelhak, Kamel Monastiri, Nicolas Levy, Anachiara de Sandre-Giovannoli, Rida Murad

Background: Noonan syndrome (NS) is a relatively common autosomal dominant disorder caused by germline mutations in various genes involved in the RAS MAP kinase signaling pathway. Although clinically heterogeneous, characteristic findings include typical facies, short stature, chest deformities, and congenital heart disease.

Methods: Here we present the clinical and molecular characteristics of Tunisian patients with NS. Using targeted next-generation sequencing, we performed a comprehensive mutation analysis of 29 genes belonging to or encoding interactors of the RAS pathway.

Results: As a result,A novel pathogenic substitution affecting LZTR1 was identified , which has been reported in only five cases of NS.

CONCLUSIONS: This report confirms that LZTR1 is involved in Noonan syndrome. Next-generation sequencing appears to be a suitable method for mutation detection in clinically and genetically heterogeneous syndromes such as NS.