hrp0086fc8.2 | Growth: Clinical | ESPE2016

Whole Exome Sequencing can Identify Defects not Detected by Candidate Gene Sequencing in Patients with Short Stature and Features of Growth Hormone Insensitivity (GHI)

Shapiro Lucy , Savage Martin , Davies Kate , Metherell Lou , Storr Helen

Background: GH insensitivity (GHI) encompasses growth failure, low serum IGF-1 and normal/elevated serum growth hormone (GH) (basal level >5 μg/L and/or peak on provocation testing >10 μg/L). In a significant number of children the molecular cause is unknown.Objective: To investigate the genetic etiology of GHI in a cohort of children by candidate gene (CGS) and whole exome (WES) sequencing.Methods: About 109 pati...

hrp0084fc5.3 | Endocrine Oncology/Turner | ESPE2015

Screening in Children with Succinate Dehydrogenase B (SDHB) Mutations: a Single Centre’s Family Clinic Experience

Shapiro Lucy , Srirangalingam Umasuthan , McAndrew Lorraine , Martin Lee , Tufton Nicola , Kumar Ajith , Drake William , Akker Scott , Storr Helen

Background: Germline mutations in SDHB gene are associated with the familial paraganglioma (PGL) syndrome that carries the highest malignant potential. Although penetrance is lower than initially described, lack of effective treatments for metastatic PGLs makes screening essential for early tumour detection, surgical removal and improved outcome. However, no consensus exists in relation to timing and mode of screening.Objective: To assess publis...

hrp0084p2-183 | Adrenals | ESPE2015

24-H Urinary Free Cortisol as a Screening Test for Cushing’s Syndrome in Children

Shapiro Lucy , Elahi Shezan , Baliey Joe , Perry Les , Martin Lee , Grossman Ashley , Akker Scott , Monson John , Drake William , Savage Martin , Storr Helen

Background: Cushing’s syndrome (CS) in children remains a challenge to diagnose and exclude. Published diagnostic guidelines for CS are heavily based upon adult data. The use of 24-h urinary free cortisol (UFC) measurements in the diagnosis of adult CS may have limited use. There is little data on the utility of 24-h UFC in children.Objective and hypotheses: We hypothesised that 24-h UFC is a robust and reliable screening test in children. The study...

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...