Partial growth hormone insensitivity and dysregulatory immune disease associated with de novo germline activating STAT3 mutations.

ABSTRACT: Germinal heterozygous activating STAT3 mutations represent a novel monogenic defect associated with multi-organ autoimmune disease and, in some cases, severe growth retardation. By using whole-exome sequencing, we identified two novel STAT3 mutations, p.E616del and p.C426R, in two unrelated pediatric patients with IGF-I deficiency and immune dysregulation. The functional analyses showed that both variants were gain-of-function (GOF), although they were not constitutively phosphorylated. They presented differences in their dephosphorylation kinetics and transcriptional activities under interleukin-6 stimulation. Both variants increased their transcriptional activities in response to growth hormone (GH) treatment. Nonetheless, STAT5b transcriptional activity was diminished in the presence of

SUBMITTER: Gutierrez M 

PROVIDER: S-EPMC6143347 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature