Endocrine Abstracts

Ectopic (or ‘illegitimate’) transcripts, which have been widely used to study disease-causing mutations when samples from the appropriate tissue cannot be obtained, are generally faithful representations of the normal tissue-specific counterparts. Here, we report the occurrence of ectopic transcripts of the hepatocyte nuclear factor-1 beta (HNF-1β) gene, mutations of which may result in maturity onset diabetes of the young type 5 (MODY5), the renal cysts ...

Parafibromin is a tumour suppressor protein, encoded by the gene responsible for the hyperparathyroidism-jaw tumour (HPT-JT) syndrome, which is an autosomal dominant disorder, characterised by parathyroid tumours, ossifyfing fibromas, renal and uterine tumours. Parafibromin is a component of the polymerase-associated factor 1 (PAF1) complex and interacts directly with β-catenin, although these functions do not fully explain its role in tumourigenesis. To further investiga...

MicroRNAs are highly conserved non-coding RNAs that regulate diverse cellular processes. Altered microRNA expression is observed in many human cancers and microRNAs may have tumour suppressor or oncogenic properties. One group of putative tumour suppressor microRNAs is the let-7 family whose expression is reduced in several human tumours, and which inhibit the expression of several oncogenes including HMGA2 and K-Ras. Let-7 expression have also been observed to b...

Background: Mutations in the UMOD gene, which encodes the Tamm-Horsfall Glycoprotein (THP), cause FJHN, an autosomal dominant disorder characterised by gout and renal failure. THP is a 640 amino acid glycosylphosphatidylinositol-anchored protein, containing three Epidermal Growth Factor (EGF)-like domains, a cysteine-rich region and a Zona Pelllucida (ZP) domain. THP is translated into the Endoplasmic Reticulum (ER) lumen, glycosylated in the Golgi apparatus, trafficked...

Delayed puberty may occur in some boys affected with X-linked Spondyloepiphyseal dysplasia tarda (SEDT), which is caused by mutations of the gene encoding a 140 amino acid protein designated Sedlin. Sedlin interacts with the pituitary homeobox 1 (Pitx1) and steroidogenic factor 1 (SF1) transcription factors, which are involved in the development and regulation of the hypothalamic-pituitary-gonadal axis. We have therefore investigated the hypothesis that SEDT associated mutatio...

Objective: To investigate a family with the unusual combination of Multiple Endocrine Neoplasia (MEN1) and the McCune-Albright syndrome for mutations of the MEN1 and GNAS1 genes. MEN1 is an autosomal dominant disorder characterised by parathyroid, pancreatic and pituitary tumours whereas the McCune-Albright syndrome is a sporadic disorder characterised by polyostotic fibrous dysplasia, skin pigmentation and hyperfunctioning endocrine tumours.<p class="abstext...

Introduction: IIH is associated with hypo and hyperthyroidism. We report a case of IIH where the likely precipitant was the treatment for hypothyroidism itself, levothyroxine, and the challenges this presents.Case: A 14-year-old girl was diagnosed with primary hypothyroidism following investigations for short stature (height 137 cm < 0.4th centile). Serum assay showed TSH 538 mU/l (0.55–4.78 mU/l), T4 0.68 pmol/l, (1.7–22.7 pmol/...

Cyclic Cushing’s syndrome (CCS) is a rare condition that involves recurring episodes of hypercortisolaemia, alternating with normocortisolemia at intervals ranging from a few days to several years. To diagnose CCS, it is necessary to demonstrate three cortisol peaks and two troughs. CCS is mostly seen in females and can be Adrenocorticotropic hormone (ACTH)-dependent or independent2. The common causes of CCS are Cushing’s Disease (55% ), ectopic ACTH syndrome (26%), ...

Marshall-Smith syndrome (MSS) is a congenital disorder affecting skeletal and neural development, due to mutations in the nuclear factor I/X (NFIX) gene. NFIX encodes a ubiquitously expressed transcription factor that regulates the expression of viral and cellular genes. To identify novel genes that are misregulated by NFIX mutations, RNA sequencing and proteomics analyses were performed on mouse embryonic fibroblast (MEF) cells derived from a repres...

Case history: Idiopathic Infantile Hypercalcaemia (IIH) classically presents in the first year of life, usually resolves by 1 year of age and is due to mutations in 1,25-dihydroxyvitamin D2 24-hydroxylase (CYP24A1) or, rarely, sodium-phosphate cotransporter-2A (SLC34A1). We report a case of IIH in a Caucasian female, who was born to non-consanguineous parents, with hypercalcaemia, hypercalciuria and associated complications persisting into adulthoo...