Endocrine Abstracts

Background: The insulin receptor (INSR) is alternatively spliced in a developmental and tissue specific manner into two isoforms, IR-A and IR-B. IR-A excludes exon 11 and is widely expressed whereas IR-B includes exon 11 and is expressed in insulin sensitive tissues. The severe short stature disorder 3-M syndrome is caused by mutations in CUL7, OBSL1 and CCDC8 and we have recently associated these proteins with the major mRNA splicing pathways includ...

Introduction: 3-M syndrome is associated with mutations in CUL7, OBSL1 and CCDC8 with the three proteins interacting within a novel growth pathway. The impact of this pathway on cellular growth has not been fully defined. We have shown that i) GH and IGF1 signalling are altered; ii) IGF2 expression is reduced and iii) expression of insulin receptor isoforms are altered in 3-M fibroblasts.Aim: To characterise the activa...

Background: Many children with short stature (defined as height SDS <−2 S.D.) have no identified cause for their growth impairment and are classified as either small for gestational age (SGA) or idiopathic short stature (ISS) depending on birth size. Adult height is a polygenic trait and has been associated with >180 single nucleotide polymorphisms (SNPs) to date. We hypothesized that sequence variants (SNPs or insertion/deletions (indels)) in cand...

Background: 3-M syndrome is an autosomal recessive disorder characterized by pre- and post-natal growth restriction, normal intelligence and dysmorphic facial features. Mutations in the genes encoding Cullin 7 (CUL7) and Obscurin like-1 (OBSL1) have been shown to cause 3-M syndrome.Aims: To characterize CUL7 production and localization in a primary fibroblast cell line from a patient with 3-M syndrome due to a CUL7 mutation and to assess cell prol...