Endocrine Abstracts

Whilst the rise in the prevalence of obesity has been driven by environmental factors, there is considerable evidence that body weight and fat mass are highly heritable traits. Differences in susceptibility to obesity between individuals have strong genetic determinants.Our strategy has been based on studies of patients with severe obesity where we hypothesised that major highly penetrant genetic variants were likely to be playing an important role.<...

Abstract unavailable....

The identification and characterization of patients with morbid obesity due to mutations in single genes has shed light on the molecular mechanisms underlying the hypothalamic regulation of appetite, body weight and endocrine axes.Two severely obese cousins in a consanguineous family were found to have undetectable levels of serum leptin and were homozygous for a frameshift mutation in the ob gene. These children were severely hyperphagic, constantly dem...

Introduction: Thyroid hormones act via receptors encoded by different genes (THRA and THRB) generating receptor subtypes (TRα1, TRβ1, TRβ2) with differing, tissue-specific expression. Resistance to Thyroid Hormone due to THRB defects is well recognised, but no THRA mutations have yet been reported. We describe the first case of human TRα-mediated thyroid hormone resistance due to a dominant negative THRA mutation.Results: A 6-year-old...