CEDIE   05498
CENTRO DE INVESTIGACIONES ENDOCRINOLOGICAS "DR. CESAR BERGADA"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Functional characterization of two novel STAT3 mutations associated to partial GH insensitivity.
Autor/es:
SCAGLIA P; DOMENE H; RAMIREZ URREA L; JASPER H; KARABATAS L; GUTIERREZ M
Lugar:
Buenos Aires
Reunión:
Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017
Institución organizadora:
SAIC, SAIB, SAI, SAA, SAB, SAFE, SAFIS, SAH, SAP
Resumen:
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