Functional characterization of two novel STAT3 mutations associated to partial GH insensitivity.

SCAGLIA P; DOMENE H; RAMIREZ URREA L; JASPER H; KARABATAS L; GUTIERREZ M

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

SAIC, SAIB, SAI, SAA, SAB, SAFE, SAFIS, SAH, SAP

FUNCTIONAL CHARACTERIZATION OF TWO NOVELSTAT3 MUTATIONS ASSOCIATED TO PARTIAL GHINSENSITIVITY.Laura Ramírez Urrea, Paula Scaglia, Liliana Karabatas,Héctor Jasper, Horacio Domené, Mariana GutiérrezCentro de Investigaciones Endocrinológicas ?Dr. César Bergadá?(CEDIE) CONICET - FEI - División de Endocrinología,Hospital de Niños Ricardo Gutiérrez.Abstract: Germinal heterozygous activating STAT3 mutations representa novel monogenic defect associated with multi-organ autoimmunedisease and severe growth retardation. Here, we aimedto characterize two novel STAT3 variants, p.E616del and p.C426R,identified by whole-exome sequencing in two unrelated pediatric patientswith insulin like growth factor (IGF)-1 deficiency and immunedysregulation. STAT3 gene variants were generated by site-directedmutagenesis and transfected into HEK293T cells. The impact ofthese variants on STAT3 expression, phosphorylation and activitywas study using a luciferase reporter system and by Western Immunoblot.The functional analyses showed that both variants weregain-of-function (GOF), although they were not constitutively phosphorylated.While both variants increased their transcriptional activitiesin response to GH (p