In Vitro Characterization Of Two STAT3 Gain Of Function Mutations Associated With IGF-1 Deficiency And Immune Dysregulation.

GUTIERREZ, MARIANA; SCAGLIA, PAULA; MARTUCCI, LUCIA; KARABATAS, LILIANA; DOMENE, SABINA; BLANCO, MIGUEL; SANGUINETTI, NORA; BEZRODNIK, LILIANA; DI GIOVANNI, DANIELA; CALDIROLA, MARIA SOLEDAD; ESNAOLA AZCOITI, M; JONES, N; HWA, VIVIAN; REVALE, SANTIAGO; VAZQUEZ, MARTIN; JASPER, HECTOR; KUMAR, ASHISH; DOMENE, HORACIO

Buenos Aires

Congreso; Sociedad Latinoamericana de Endocrinologia Pediatrica (SLEP); 2016

We have recently reported two heterozygous de novo mutations, c.1847_1849delAAG (p.E616del) and c.1276T>C (p.C426R), in the STAT3 gene in children with severe growth failure associated with a spectrum of early-onset autoimmune disease. The aim of the present study was to characterize in vitro the effects of interleukin (IL)-6 (20 ng/mL) and growth hormone (GH) (200 ng/mL) on the expression, phosphorylation and transcriptional activity of WT-STAT3 and these two variants. STAT3 gene variants were generated by site-directed mutagenesis and transfected into HEK293T cells. The activity of each mutant was evaluated using a STAT3-responsive dual-luciferase reporter assay. Expression of both newly identified mutants resulted in a significant increase in reporter activity (p