Endocrine Abstracts

Multiple endocrine neoplasia type 1 (MEN1) is characterized by the combined occurrence of parathyroid, pancreatic islet and anterior pituitary tumours. Over 95% of MEN1 patients will have developed a manifestation of MEN1 by the age of forty years, and in >85% of patients, parathyroid tumours are the first to occur. In a previously reported Men1 knockout mouse model, parathyroid tumours occurred in less than 50% of Men1 heterozygous (Men1+/−...

Pituitary tumours occur in more than 40% of multiple endocrine neoplasia type 1 (MEN1) patients, and these are more aggressive and difficult to treat than those in non-MEN1 patients. Assessments of in vivo proliferation rates will be of importance in evaluating emerging treatments. We have used the uptake of the DNA nucleotide precursor, 5-bromo-2-deoxyuridine (BrdU), to assess proliferation rates of pituitary tumours in our Men1 knockout mouse model, which devel...

Autoimmune polyendocrinopathy type 1 (APS1) is an autosomal recessive disorder characterised by hypoparathyroidism, adrenocortical failure, and mucocutaneous candidiasis. The gene causing APS1 is the autoimmune regulator (AIRE-1) gene, which maps to 21q22.3 and consists of 14 exons. The AIRE-1 protein, comprising of 545 amino acids, contains two PHD zinc-finger motifs, a proline rich region and four LXXLL motifs, consistent with its role as a transcription factor. Over 25 diff...

SEMDs are a heterogeneous group of skeletal disorders characterised by defective growth and modelling of the spine and long bones. Genetic defects in two inherited SEMDs have been identified and these involve abnormalities of the collagen type II gene located on chromosome 12q12-q13.2, and an ATP sulfurylase/APS kinase gene located on 10q23-34. These are not the cause of the Missouri variant (SEMDMO), which occurs as an autosomal dominant trait in a unique four-gene...

X-linked recessive hypoparathyroidism (XLHPT), due to congenital parathyroid agenesis, has been reported in two related kindreds from Missouri, USA. Affected individuals, who are males, suffer from epilepsy due to hypocalcaemia during infancy, whilst the females are normocalcaemic. Studies have mapped XLHPT to chromosome Xq27 and defined a 1.5 Mbp interval flanked centromerically by Factor IX and telomerically by DXS984. DNA sequence analysis of 4 candidate genes (proto-dbl, A...

(This poster is based on OC3)...

Hereditary multiple exostosis (HME) is an autosomal dominant disorder characterised by the development of benign cartilage-capped tumours, located at the juxtaepiphyseal regions of long bones. Patients suffer from short stature and skeletal deformities and may occasionally develop chondrosarcomas or osteosarcomas.HME is a genetically heterogeneous disorder and three loci referred to as EXT1, EXT2 and EXT3 have been mapped to chromosomes 8q24.1, 11p11-12...

Calcium sensing receptor (CaSR) mutations may result in either hypocalciuric hypercalcaemia or hypocalcaemic hypercalciuria due to a loss or gain of function, respectively. It has also been postulated that some gain of function CaSR mutations may result in idiopathic (i.e. normocalcaemic) hypercalciuria (IH). We reasoned that such CaSR mutations would lead to an early onset of IH and have sought for them in 12 unrelated children who were normocalcaemic and developed IH nephrol...

The calcium sensing receptor (CaSR) plays a central role in altering the secretion of parathyroid hormone (PTH) in response to alterations in extracellular calcium, and four studies have reported an association between CaSR polymorphisms and serum Ca 2+, serum PTH, and bone mineral density (BMD). However, two other studies have failed to detect such associations. We have therefore undertaken studies to investigate the Ala986Ser, Arg990Gly, and Gln1011Glu CaSR polymo...

Gout, which is commonly associated with hyperuricaemia, affects 0.2% of the population. Hyperuricaemia has a heterogeneous aetiology that may be due to either over production and/or reduced renal clearance, of urate. In order to identify the mechanisms underlying reduced excretion of urate, we undertook positional cloning studies of familial juvenile hyperuricaemic nephropathy (FJHN), which is an autosomal dominant disorder characterised by hyperuricaemia, a low fractional ren...