hrp0086p2-p90 | Adrenal P2 | ESPE2016

A Genetic Diagnosis of Familial Glucocorticoid Deficiency Resulting in Cessation of Long-term Mineralocorticoid Treatment in Three Siblings

Cottrell Emily , Mushtaq Talat

Background: Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder characterised by ACTH resistance and leads to isolated glucocorticoid deficiency. Mutations in the gene encoding the ACTH receptor (MC2R) are responsible for around 25% of cases.Case report: The female index case was hyperpigmented at birth. At one week of age her ACTH level was >1200 ng/ml, plasma renin activity (PRA) 11.4 pmol/ml/h with an aldosterone of 520...

hrp0084p2-261 | Diabetes | ESPE2015

Gaining from Patient Experience on a Local Level: The Introduction of Annual Questionnaires for Children and Teenagers with Diabetes

Cottrell Emily , Chandwani Manju , Hanson Frances , Wong James

Background: The children and teenage diabetes team currently care for 270 patients in the region and includes speciality doctors, specialist nurses, dieticians and psychologists.Objective and null hypothesis: To evaluate the strengths and weaknesses of the local care provided by the team, and learn from current patient experience.Method: An anonymous questionnaire was completed by diabetic patients aged 9–20 years when attendi...

hrp0092p3-167 | Growth and Syndromes (to include Turner Syndrome) | ESPE2019

Bloom Syndrome in 7-Year-Old Girl Diagnosed with Short Stature

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

Introduction: Bloom syndrome (BS) is a rareautosomal recessive disorder caused by mutations in the BLM gene, located on the long arm of the chromosome 15 (15q26.1). The typical symptoms of the disease are short stature, low birth weight, dysmorphic features including long, narrow face (dolichocephaly), micrognathism and prominent nose and ears. Other characteristic features include a rash following sun exposure, hyper-pigmented areas or cafe-au-lait s...

hrp0086p1-p27 | Adrenal P1 | ESPE2016

Beckwith-Wiedemann Syndrome and Bilateral Phaeochromocytoma: A Diagnostic Challenge

Cottrell Emily , Glaser Adam , Blackburn Mike , Alvi Sabah , Mushtaq Talat , Squire Roland , Steele Caroline

Background: Beckwith-Wiedemann Syndrome (BWS) is a rare overgrowth disorder secondary to various mutations in growth-regulatory genes on chromosome 11p15.5. A well-established association exists between BWS and both benign and malignant tumours, most commonly Wilms’ tumour and hepatoblastoma. We present a less frequently described diagnosis of bilateral phaeochromocytoma in association with BWS.Case report: We report the case of a 14-year-old girl w...

hrp0089lb-p1 | Late Breaking P1 | ESPE2018

A Second Growth Hormone Receptor Pseudoexon Mutation Causing Frameshift and Severe Postnatal Growth Failure

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

Background: Growth Hormone Insensitivity (GHI) is usually caused by mutations in the Growth Hormone receptor (GHR). Patients present with short stature associated with high GH and low IGF-I levels and often have midfacial hypoplasia (typical Laron syndrome facial features). Our centre previously described the first GHR pseudoexon mutation (42700896A>G, c. 618+792A>G). The inclusion of this 108bp pseudoexon is predicted to lead to in-frame insertion of...

hrp0094p1-179 | Growth Hormone and IGFs B | ESPE2021

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) encompasses normal/elevated growth hormone (GH), low IGF-I levels and growth restriction. Non-classical/mild-moderate GHI is an emerging entity which is poorly characterised, and, in many subjects, the underlying cause is unclear. Heterozygous dominant negative (DN) variants located in the intracellular/transmembrane domain of the GH receptor (GHR) cause a ‘non-classical’ GHI phenotype.<p class="abst...

hrp0095p1-101 | GH and IGFs | ESPE2022

A rare heterozygous IGFI variant causing impaired IGF-I cleavage and postnatal growth failure: a novel disease mechanism with insights into IGF-I physiology

Cottrell Emily , Andrews Afiya , Williams Jack , Chatterjee Sumana , Edate Sujata , A. Metherell Louise , Hwa Vivian , L. Storr Helen

Background: Pathogenic IGFI gene mutations causing childhood growth failure are rare. Only 5 autosomal recessive mutations, one IGFI copy number variant and 2 heterozygous frameshift mutations are reported. Heterozygous missense IGFI mutations have not previously been described.Objectives: To identify and functionally characterise a novel missense IGFI variant in a patient with postnat...

hrp0092rfc14.4 | Adrenals and HP Axis | ESPE2019

GHR Transcript Heterogeneity May Explain the Phenotypic Variability in Patients with Homozygous GHR Pseudoexon (6ψ) Mutation

Chatterjee Sumana , Rose Steven J , Mushtaq Talat , Cottrell Emily , Maharaj Avinaash V , Williams Jack , Savage Martin O , Metherell Loiuse A , Storr Helen L

Objectives: The homozygous GHR pseudoexon (6ψ) mutation leads to aberrant splicing of the GHR gene with clinical and biochemical heterogeneity. We investigated whether the phenotypic variability could be explained by transcript heterogeneity i.e. ratio of abnormal (6ψ GHR) to normal (WT GHR) transcripts and/or the presence of concurrent defects in other short stature (SS) genes.Methods: 6&#968...

hrp0094p2-287 | Growth and syndromes (to include Turner syndrome) | ESPE2021

Novel LZTR1 mutations in subjects with features of Noonan Syndrome and GH insensitivity negatively regulate GH-induced IGF-I production and hyperactivate GH-induced ERK1/2 activation in response to GH in vitro

Chatterjee Sumana , Romeo Bertola Debora , Agwu Chizo , Maharaj Avinaash , Williams Jack , Cottrell Emily , Shapiro Lucy , Andrews Afiya , Savage Martin O. , Gaston-Massuet Carles , Metherell Louise A. , Storr Helen L. ,

Background: Noonan Syndrome (NS) can overlap clinically and biochemically with growth hormone insensitivity [GHI; short stature (SS), low IGF-I and normal/elevated GH levels]. Mutations in multiple genes regulating RAS/MAPK pathway have been identified in NS including LZTR1 variants. Function of LZTR1 is poorly understood and its role in growth retardation is unknown.Objectives: To functionally characte...

hrp0095p1-110 | Growth and Syndromes | ESPE2022

Characterisation of the first heterozygous missense HMGA2 variant helps delineate the crucial functional roles of a novel growth gene

Cottrell Emily , V. Maharaj Avinaash , Triggs-Raine Barbara , Thanasupawat Thatchawan , Williams Jack , Fujimoto Masanobu , A. Metherell Louise , Hwa Vivian , Klonisch Thomas , Hombach-Klonisch Sabine , L. Storr Helen

Background: Silver Russell syndrome (SRS) is genetically heterogenous and around 30% of patients with clinical SRS have no genetic diagnosis. Mutations in HMGA2 have recently been identified causing growth failure and an SRS-like phenotype. Despite strong evidence of the crucial role of HMGA2 in growth across species, the mechanism of action of HMGA2 in human linear growth is unclear.Objective:...