In vitro Characterization of Two STAT3 Gain of Function Mutations Associated with IGF-1 Deficiency and Immune Dysregulation

SCAGLIA, PAULA; KARABATAS, LILIANA; NORA SANGUINETTI; MARÍA SOLEDAD CALDIROLA; VIVIAN HWA; HÉCTOR JASPER; MARIANA GUTIÉRREZ; LUCIA MARTUCCI; MIGUEL BLANCO; DANIELA DI GIOVANNI; NANA HAWA JONES; MARTÍN VÁZQUEZ; HORACIO M DOMENE; KESELMAN, ANA; SABINA DOMENE; LILIANA BEZRODNIK; ESNAOLA AZCOITI, MARÍA; SANTIAGO REVALE; ASHISH KUMAR

Buenos Aires

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

Sociedad Latinoamericana de Endocrinología Pediátrica

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 earlyonset autoimmune disease. Theaim 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 WTSTAT3 and these two variants. STAT3 gene variants were generated by sitedirected mutagenesis and transfected into HEK293T cells. The activity of each mutant was evaluated using a STAT3responsive dualluciferase reporter assay. Expression of both newly identified mutants resulted in a significant increase in reporter activity (p