Endocrine Abstracts

ApoB isoforms are components of the chylomicron, and of the atherogenic LDL and Lp(a) particles. Ex26 is exceptionally long at 7.57kb as most exons are <500bp. Ex26 is also the site of RNA editing, which generates the ApoB48 isoform instead of ApoB100. The first 3kb of ex26 contains 15 sequences matching the splice site consensus, which could be used in splicing, but are not. Splice sites matching the consensus but which are not used are called pseudosites. How the spliceos...

Background: The growth hormone receptor (GHR) 6Ψ pseudoexon mutation (A to G at ds-1) is one of the most frequent mutations causing GH insensitivity. It causes aberrant mRNA splicing, leading to activation of a pseudoexon and insertion of 36 additional amino acids, resulting in a functionless receptor. Although IGF-I remains the mainstay of treatment for these patients we investigated the ability of RNA antisense oligonucleotides (ASOs) to correct aberrant GHR splicing us...

Pseudoexons resemble true exons by current bioinformatic criteria and may outnumber true exons by 10:1. They are, however, never spliced into mature mRNA. A point mutation in the GHR gene results in abnormal splicing of a pseudoexon, leading to Laron syndrome. The GHR pseudoexon lies between exons six and seven and the point mutation is adjacent to the pseudoexon 5' splice site.Our studies aimed to define the elements that normally prevent splicing of this pseudoexon.A...

Introduction: Insulinomas are the most common, functioning, pancreatic neuro-endocrine tumours. The minority of patients <10% who present with metastatic disease have a median survival of <2 years.We present a case of a gentleman with a 30 years history of Multiple Endocrine neoplasia type 1 (MEN1), which highlights the various modalities of treatment and the challenges from his progressive disease and marked symptomatic hypoglycaemia.<p clas...

Growth hormone insensitivity, also known as Laron Syndrome (LS), is caused by mutations within the GH receptor (GHR). A 1.5 year-old boy with consanguineous parents was referred with postnatal linear growth failure (length 64 cms, minus 6 SDS). Facial features were typical of LS. Investigation revealed elevated serum GH (1145 mIU per litre) and low IGF-I (4 nmol per litre). Genomic DNA was isolated from peripheral blood leucocytes and all GHR exons, including intron-exon bound...

We describe the case of a 48-year-old woman, who presented with a history of six months' weight gain, easy bruising and difficulty in rising from a seated position. Examination revealed typical clinical features of Cushing's syndrome. She was hypertensive at 150/100 mmHg and diabetic. She was also agitated, emotionally labile, and disinhibited, requiring sedation. Her sister has MEN-1 (hyperparathyroidism and lung carcinoid tumour).Low-dose and high-dose...

Background: It is often difficult to define the clinical relevance of a novel gene variant. In silico analyses of variants located close to exon–intron-junctions are utilised to predict the result of these basepair changes. We have previously identified two splice-site variants in AIP and confirmed the predicted changes for c.249G>T, p.G83AfsX15 and c.807C>T. We identified the c.469-2A>G heterozygous variant located at the end of intron-3 in a childhood...

Background: Mutations in succinate dehydrogense-B (SDH-B) or von Hippel Lindau (VHL) genes can result in chromaffin tumours.Objective: To compare the clinical phenotypes of subjects developing chromaffin tumours as a result of SDH-B or VHL mutations.Subjects: Thirty-one subjects with chromaffin tumours. Sixteen subjects had SDH-B gene mutations and 15 subjects had a diagnosis of VHL.<p ...