ESPE Abstracts

Background: Recently, a new monogenic cause of multiple immune system disorders and short stature has been attributed to germline activating mutations in the STAT3 gene encoding signal transducer and activator of transcription 3. Possible pathophysiological mechanisms include enhanced proliferation and activation of T-helper 17 cells and inhibition of regulatory T-cells by STAT3, as described in in vitro studies.Case presentation: The a...

Background: Congenital Hyperinsulinism (CHI) is a heterogeneous genetically determined condition that is characterised by unregulated secretion of insulin from pancreatic β-cells. The most common and severe cases are caused by mutations in the ABCC8 gene encoding the SUR1 subunit of the KATP channel subunit. To assess the pathogenic effect of novel ABCC8 mutations we performed in-vitro functional studies.Objective and hy...

Background: Recently a heterozygote mutations in the gene ACAN coding the protein aggrecan has been described as a cause of familiar short starture combined with accelerated bone age. The aggrecan is an extracellular proteoglycan in cartilage of growth plates and plays an important role in biological and biomechanical properties of cartilage.Objective and hypotheses: To provide a genetic screening of ACAN within the families with familiar short stature a...

Background: Short stature homeobox-containing gene (SHOX) is located within the pseudoautosomal region 1 (PAR1) of the sex chromosomes. SHOX mutations and PAR1 deletions encompassing SHOX or its upstream/downstream enhancers have been identified in ~60% of Léri-Weill dyschondrosteosis (LWD) and ~5–15% of idiopathic short stature (ISS) patients. Recently SHOX duplications have been described in LWD/ISS individuals.Case presentation: The boy was ...

Background: Mutations in the SUR1 subunit of the KATP channel encoded by the ABCC8 gene can result in diverse phenotypes ranging from Transient Neonatal Diabetes (TNDM) to type 2 diabetes in adulthood. These patients may benefit from sulphonylurea treatment.Objective and hypotheses: To describe the course of diabetes in two families with ABCC8 gene mutations and to assess the effect of sulphonylurea treatment.<p class="ab...

Background: Congenital hyperinsulinism of infancy represents a group of heterogeneous disorders characterized by over-secretion of insulin from pancreatic β cells causing severe hypoglycemia. Genetically, congenital hyperinsulinism is caused by defects in key genes regulating insulin secretion (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, UCP2, HNF4A, and non-constantly HNF1A). The aim of our pr...

Background: Congenital Hyperinsulinism (CHI) is a common cause of persistent hypoglycaemia in the neonatal and infant period. It is most commonly caused by mutations in one of the KATP channel subunits, either SUR1 encoded by the gene ABCC8 or Kir6.2 encoded by the gene KCNJ11. Patients carrying mutations in the ABCC8 and KCNJ11 genes simultaneously have not been reported yet.Objective and hypotheses: Our aim was to describe the clinical pheno...

Background: Neonatal hyperinsulinaemic hypoglycaemia (HH) has recently been recognized as a consequence of mutations in HNF1A, which also cause maturity-onset diabetes of the young (MODY) later in life.Aims: To report phenotypic and genetic investigations of two patients with functional characterisation of identified mutations in HNF1A.Case reports: Two unrelated patients presented with HH requiring i.v. glucose a...

Background: The phenotype associated with heterozygous HNF1A gene mutations has recently been extended to include neonatal hyperinsulinaemic hypoglycaemia (HH) in addition to maturity-onset diabetes of the young (HNF1A–MODY).Objective and hypotheses: The baby boy was born at 38th week of gestation; BW 4110 g; BL 53 cm (LGA). The mother had gestational diabetes; her father is treated for diabetes mellitus from the age of 50 years. The boy de...

Background: Microdeletions of 14q22q23 have been associated with eye abnormalities. Other symptoms in deletion carriers are less well recognized.Objective and hypotheses: We focused on growth characteristics and response to GH treatment in two unrelated children with 14q22q23 deletions.Method: Array comparative genomic hybridisation (aCGH).Results: Both patients displayed bilateral anophthalmia. Their brain M...