ESPE Abstracts

Introduction: Impaired insulin sensitivity (IS) is a hallmark of increased cardiometabolic risk in adolescents with obesity. Surrogate markers of IS based on fasting insulin have important limitations. The Single-Point Insulin Sensitivity Estimator-Index (SPISE), obtained using the mathematical formula 600 × HDL-C^0.185/Triglycerides^0.2 × BMI^1.338, has been shown to be a predictor for detecting both insulin resistance and the risk of developing g...

Introduction: The Androgen Receptor (AR) is a steroid hormone receptor. Upon activation by its potent ligand, 5-alpha-dihydrotestosterone (DHT), it regulates the expression of target genes leading to the development of the outer male genitalia. Mutations in the AR gene are associated with Androgen Insensitivity Syndrome (AIS), characterized by the presence of testes and varying degrees of undervirilization of the external genitalia. Since many individ...

Objectives: The Kabi/Pfizer International Growth Study (KIGS) was the largest and longest running international database of pediatric patients receiving recombinant human growth hormone (rhGH). The objective of the current analysis is to describe the dosage of rhGH at enrolment into KIGS according to diagnosis and geographical region.Methods: Between 1987-2012, 83,803 pediatric patients were enrolled into KIGS if they re...

Introduction: The first patient with Temple syndrome (TS, ORPHA 254516) was described in 1991. The genetic condition is rare (prevalence<1/1000 000, <100 described patients). An abnormal expression of genes in the imprinted 14q32.2 region has been revealed. The 14.32.2 region is characterized by three differentially methylated regions (DMRs) and a cluster of paternally and maternally expressed genes. Main clinical features are growth delay (pre-and postn...

Type 1 diabetes mellitus is a chronic disease of autoimmune etiology that is highly prevalent in childhood. In the last decade, the possibility of using the Bacillus Calmette-Guérin vaccine for the treatment of this disease has been studied thanks to its immunomodulatory action. These authors published a few years ago an inconclusive work on the influence of the use of BCG on the number of cases observed in the CCAA in a smaller cohort (Bol S Vasco- Nav Pediatrician 202...

Background: Kinase suppressor of Ras 2 (KSR2) gene codes for a scaffold protein modulating intracellular pathways that involve MEK/BRAF cascade and AMPK signaling. KSR2 plays an important role in energy balance regulation, and KSR2 mutations were reported to be associated with obesity and insulin resistance in mice and humans. In transfected cells, several KSR2 mutations lead to impaired fatty acid oxidation, which improved under met...

Background: Hypothalamic obesity (HyOb) is a disease characterized by weight gain resistant to lifestyle changes and dietary restriction. The main clinical findings are hyperfagia and decline of satiety, high levels of insulin and an increase of adipogenesis. The major problem for these patients is that conventional treatments, either medical or surgical are not succesful and have variable results.Objective and hypotheses: We aim to describe the natural ...

Background: In a large fraction of patients with clinically presumed Androgen Insensitivity Syndrome, no mutation of the Androgen Receptor gene can be detected. However, established Sanger sequencing techniques of the AR gene are often limited to the coding region.Objective and Hypotheses: To set up a next generation sequencing (NGS) approach of the entire AR locus (including UTRs, exons, introns, up- and downstream regions) for a comprehensive ...

Introduction: Androgen insensitivity syndrome (AIS) is a 46,XY difference of sex development (DSD) classically caused by mutations in the X-chromosomal androgen receptor (AR) gene. Nevertheless, in over 50% of individuals with clinical AIS no AR coding gene mutation can be found. We previously established an assay (apolipoprotein D (APOD) assay) that measures androgen dependent AR-activity in genital skin fibroblasts (GFs). Using this assay we identified a gro...

Context: Severe forms of growth hormone insensitivity (GHI) are characterised by extreme short stature, dysmorphism and metabolic anomalies. They are classically caused by homozygous or compound heterozygous mutations of the growth hormone receptor gene (GHR). Genetic analysis traditionally focuses on the exonic regions of genes that encode proteins rather than the intervening non-coding sequences. These seldom explored non-coding regions may harbour ...