Endocrine Abstracts

Previously we reported two loss-of-function dominant negative mutations (P467L, V290M) in human peroxisome proliferator-activated receptor gamma (PPARg) in three individuals with severe insulin resistance, early onset type 2 diabetes mellitus (T2DM) and hypertension. Subsequent detailed clinical and radiological evaluation of these subjects has revealed that each exhibits a stereotyped pattern of partial lipodystrophy affecting the limbs and buttocks. Recently a female with pa...

Primary hyperparathyroidism (HPT) is most frequently encountered as a non-familial disorder, but 10% of patients with primary HPT will have a hereditary form, which may occur as an isolated endocrinopathy or as part of a complex tumour syndrome such as multiple endocrine neoplasia type 1 (MEN 1) or type 2 (MEN 2), or the hereditary hyperparathyroidism-jaw tumour syndrome (HPT-JT). Familial isolated hyperparathyroidism (FIHP) is an autosomal dominant disorder characterised by u...

The nuclear receptor PPARgamma is important for biological processes including adipogenesis and glucose homeostasis. In subjects with severe insulin resistance, we have previously reported two types of human PPARgamma gene defect: heterozygous, missense mutations (P467L, V290M) in the ligand binding domain (LBD) which inhibit wild type (WT) receptor action in a dominant negative manner by recruitment of transcriptional corepressors; or double heterozygosity for a frameshift/pr...