Endocrine Abstracts

Bone mineral density (BMD) is a highly heritable trait. We sought to investigate site and gender specificity of BMD inheritance in general pedigrees.Probands with primary osteoporosis and low BMD relative to an age- and sex- matched cohort (z-score <-2.0 at either lumbar spine (LS) or femoral neck (FN)) were identified from the Nuffield Orthopaedic Centre (Oxford UK) (45 male, 102 female). All available first- and second-degree relatives were recrui...

The hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome is an autosomal dominant disorder that is due to a haploinsufficiency of the zinc-finger transcription factor, GATA3 (Nature (2000) 406: 419) whose gene is located on chromosome 10p15. In order to further characterise GATA3 abnormalities we have investigated 6 HDR patients for GATA3 mutations. Leukocyte DNA samples from the 6 probands and an unrelated normal individual were used with 9 pairs of oligonucleotide...

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...

Mutations in the HSD11B2 gene explain the syndrome of apparent mineralocorticoid excess (AME), which is characterised by severe hypokalemic hypertension. The enzyme product of the HSD11B2 gene, 11-beta hydroxysteroid dehydrogenase type 2 (11beta HSD2), converts cortisol to its inactive form, cortisone. This reaction occurs primarily in the kidney, preventing the mineralocorticoid effects of cortisol, and in the placenta where it is believed to regulate fetal growth by protecti...

Objective: To construct rat congenic strains to confirm and narrow down a region on rat chromosome 2 previously implicated in blood pressure regulation. To determine expression profiles and identify differentially expressed genes between congenic strain and respective parental strain using microarray technology.Design and Methods: Total RNA was prepared from whole kidney homogenates from 2x parental SHRSPGla and 2x SP.WKYGla2a congenic rats. Expression ...

Objective: The spontaneously hypertensive stroke prone rat (SHRSP) is a model of insulin resistance and dyslipidemia. Feeding a 60% fructose diet exaggerates these phenotypes. It has been suggested that the Y chromosome may influence lipid levels in the spontaneously hypertensive rat (SHR). Therefore we examined the effects of Y chromosome on lipid phenotypes in the SHRSP after fructose feeding.Design and Methods: The S.W. Y consomic strain was construc...

A number of candidate genes have been investigated as susceptibility loci for the development of Graves' disease. Those which appear to be consistently associated with disease include the HLA and the CTLA-4 gene regions. Polymorphisms of the VDR gene have been shown to increase susceptibility to autoimmune diseases including type 1 diabetes, multiple sclerosis, and Crohn's disease. Recently, an association has also been reported between the VDR gene and autoimmune thyroid dise...

A child with short stature having height greater than 2 standard deviations below the mean for age and bone age delay of two years but with normal growth hormone secretion tests was identified. Since there was no known clinical cause of the short stature, it was decided to sequence both alleles of the patient's GH1 gene that encodes pituitary GH to determine whether there was a genetic defect responsible for the observed phenotype (with local ethical approval). A 3.2kb fragmen...