Searchable abstracts of presentations at key conferences in endocrinology

ea0077oc4.2 | Adrenal and Cardiovascular | SFEBES2021

Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause.

Argentesi Giulia , Azizan Elena , Zhou Junhua , Cabrera Claudia , O’Toole Sam , Wu Xilin , Goodchild Emily , Cottrell Emily , Marker Alison , Senanayake Russell , Garg Sumedha , Jordan Suzanne , Berney Dan , Gluck Anna , Lines Kate , Thakker Rajesh V , Tuthill Antoinette , Joyce Caroline , Karet Frankl Fiona , Metherell Lou , Teo Ada , Gurnell Mark , Parvanta Laila , Drake William , Wozniak Eva , Mein Chaz , Kinsler Veronika , Storr Helen , Brown Morris

Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. However, their frequency in aldosterone-producing cell-clusters of normal adrenals could suggest the existence of co-driver mutations which influence the development or phenotype of APAs [1]. Gain-of-function mutations in both CTNNB1 and the G-protein coupled receptor GNA11 were found by whole exome sequencing in 3/10 APAs. Further sequencing of...

ea0045oc1.2 | Oral Communications 1- CME | BSPED2016

Lysinuric protein intolerance: A cause of secondary IGF-I deficiency with raised growth hormone levels and osteoporosis

Cottrell Emily , Mushtaq Talat

A 7.7 year old girl born to consanguineous was assessed for poor growth; height −3.2 SDS, weight −2.7 SDS, BMI −0.8 SDS. Examination revealed chubby cheeks, abdominal obesity, relatively thin limbs and a suggestion of mid-face hypoplasia. There was no scoliosis or other dysmorphic features.Investigations found a 46XX karyotype and negative coeliac screen. Pituitary function testing revealed high basal Growth Hormone (GH) of 6.5 ug/l, ri...

ea0085oc2.2 | Oral Communications 2 | BSPED2022

The missing segment from the age of enlightenment

Cottrell Emily , Simpson Clare , Mushtaq Talat

Case report: An 11-year-old boy presented with an increasingly waddling gait and backache. He had been born small for gestational age (BW 1.8kg; -4.7 SDS) and had a history of dyspraxia and autism. He reported reasonable dairy intake and had no history of previous fractures or clinical signs of osteogenesis imperfecta (OI). Spinal imaging revealed multiple vertebral fractures. Malignancy and systemic inflammatory causes were excluded. An OI gene panel revealed a single pathoge...

ea0066oc4.5 | Oral Communications 4 | BSPED2019

Novel genetic defects in a cohort of Silver–Russell Syndrome (SRS) and SRS-like patients

Cottrell Emily , Ishida Miho , Moore Gudrun , Storr Helen L

Background: Silver-Russell Syndrome (SRS) is a clinically and genetically heterogenous condition. 40% patients with ‘clinical’ SRS remain without a genetic diagnosis despite fulfilling the Netchine-Harbison Clinical Scoring System (NH-CSS) criteria. There is increasing recognition of the wide range of clinical phenotypes within the SRS spectrum and overlap with other short stature syndromes.Methods: We analysed 26 undiagnosed patients with feat...

ea0074oc1 | Oral Communications | SFENCC2021

A rare heterozygous IGFI variant causing postnatal growth failure and offering novel insights into IGF-I physiology

Cottrell Emily , Chatterjee Sumana , Hwa Vivian , Storr Helen L.

Section 1: Case history: A 10-year-old girl presented with significant postnatal growth failure. Her birth weight was normal (–0.15SDS) but poor growth was observed from a few months of age. She had no other symptoms. On examination, height was –3.4SDS and head circumference –1.6SDS. She had no dysmorphic features and normal development. Section 2: Investigations: Baseline serum analyses were unremarkable. Karyotype was normal (46XX). Bone age was delayed by 2.5...

ea0066oc2.2 | Oral Communications 2 | BSPED2019

A rare but very important cause of growth failure

Cottrell Emily , Ladha Tasneem , Borysewicz-Sańczyk Hanna , Sawicka Beata , Bossowski Artur , Storr Helen L

Introduction: Bloom syndrome (BS) is a rare autosomal recessive disorder caused by mutations in the BLM gene. Classic dysmorphic features include a long, narrow face, micrognathism and prominent nose and ears. Other features of the disease include pre- and post-natal growth failure, skin rash following sun exposure, hyper-pigmented areas or cafe-au-lait lesions, high-pitched voice and immunodeficiency. The most serious complication of BS is the significant increase in...

ea0078OC6.1 | Oral Communications 6 | BSPED2021

Novel dominant negative GH receptor variants provide important insights into GH receptor physiology

Andrews Afiya , Cottrell Emily , Maharaj Avinaash , Ladha Tasneem , Williams Jack , Metherell Louise A , McCormick Peter J , Storr Helen L

Background: Growth hormone insensitivity (GHI) is a continuum defined by normal/elevated growth hormone (GH), low IGF-I levels and growth restriction. Non-classical/mild-moderate GHI is poorly characterised and is frequently underdiagnosed. Heterozygous dominant negative (DN) gene variants located in the regions encoding the intracellular/transmembrane domains of the GH receptor cause a ‘non-classical’ GHI phenotype.Hypothesis/Objective: Detail...

ea0082oc1 | Oral Communications | SFEEU2022

Genetic analysis of patients with undiagnosed short stature identified novel dominant negative GH receptor variants which provide important insights into GHR physiology

Andrews Afiya , Cottrell Emily , Maharaj Avinaash , Ladha Tasneem , Williams Jack , A Metherell Louise , J McCormick Peter , Storr Helen L

Case history: Two unrelated male patients were referred for evaluation of short stature. The first patient aged 16.5 years, had a birth weight of 2.6 kg at term (BWSDS -2.4), height 153 cm (HSDS -3.2) at referral and normal BMI SDS of 0.6. He had early postnatal hypoglycemia, which was conservatively managed, but no other significant clinical history. He had relative macrocephaly and disproportionate short stature. His mother was also short with a similar phenotype (height 147...

ea0059cc5 | Featured Clinical Cases | SFEBES2018

A second GH Receptor pseudoexon mutation causing frameshift and severe postnatal growth failure

Cottrell Emily , Maharaj Avinaash , Chatterjee Sumana , Grandone Anna , Cirillo Grazia , del Giudice Emanuele Miraglia , Storr Helen L , Metherell Louise A

Background: GH Insensitivity (GHI) is usually caused by mutations in the GH receptor (GHR). Our centre previously described the first GHR pseudoexon mutation (42700896A>G, c. 618+792A>G). Inclusion of this 108bp pseudoexon is predicted to lead to in-frame insertion of 36 amino acid residues in the dimerization domain of the GHR. This results in defective trafficking rather than impaired signalling, causing partial loss-of-function and moderat...

ea0058oc5.7 | Oral Communications 5 | BSPED2018

A novel GHR pseudoexon mutation causing frameshift and severe postnatal growth failure

Cottrell Emily , Maharaj Avinaash , Chatterjee Sumana , Grandone Anna , Cirillo Grazia , Miraglia del Giudice Emanuele , Metherell Louise A , Storr Helen L

Background: Growth Hormone Insensitivity is usually caused by mutations in the Growth Hormone receptor (GHR). Patients present with short stature, high GH levels, low IGF-I levels and typical Laron syndrome facial features. Our centre previously described the first GHR pseudoexon mutation (42700896A>G, c.618+792A>G). The inclusion of this pseudoexon is predicted to cause in-frame insertion of 36 amino acid residues between exons 6 and 7. This insertion in the ...