Searchable abstracts of presentations at key conferences in endocrinology

ea0023p8 | (1) | BSPED2009

The Current UK Experience of Recombinant IGF1 For Cases of Severe Primary IGF1 Deficiency

Mushtaq Talat , Ahmed S Faisal , Emohare Osa , Patel Leena , Rose Stephen , Shaw Nick

Background: Severe primary IGF1 deficiency (SPIGFD) is defined in children as a height less than −3sds, low IGF1 levels with normal growth hormone levels. Recombinant IGF1 (rhIGF1, Mecasermin) given twice daily as a subcutaneous injection is the only therapy available to improve the height potential in this group of children. However it may have important side effects including hypoglycaemia, growth of lymphoid tissue and injection site lipohypertrophy.<p class="abst...

ea0051oc5.6 | Oral Communications 5 | BSPED2017

Phenotypic spectrum and response to recombinant human IGF1(rhIGF1) therapy in patients with homozygous intronic pseudoexon ()GH receptor mutations

Chatterjee Sumana , Rose Stephen , Mushtaq Talat , Clayton Peter , Ten Svetlana , Bhangoo Amrit , Kumbattae Uma , Dias Renuka , Shapiro Lucy , Metherell Louise , Savage Martin , Storr Helen

Objectives: Patients with homozygous 6Ψ mutations have GH insensitivity (GHI). We previously described spectrum of clinical and biochemical phenotypes of 11 6Ψ patients (David et al. JCEM 2007;92:655) and now report 9 additional patients. Response to rhIGF-I therapy has not previously been assessed.Methods: 20 6Ψ patients (12 M, 11 families, mean age 4.0±2.2 year) were diagnosed genetically in our centre. Continuous ...

ea0058p024 | Growth | BSPED2018

Genotype–phenotype correlation in patients with homozygous GHR pseudoexon (6Ψ) mutation

Chatterjee Sumana , Rose Stephen J , Mushtaq Talat , Cottrell Emily , Maharaj Avinaash V , Williams Jack , Savage Martin O , Metherell Louise 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 Ψ GHR ...

ea0030p8 | (1) | BSPED2012

The effect of homozygosity versus heterozygosity for IGFALS gene mutations on growth, bone strength and insulin resistance

Hogler Wolfgang , Martin David , Crabtree Nicola , Barrett Timothy , Frystyk Jan , Tomlinson Jeremy , Metherell Lou , Rosenfeld Ron , Hwa Vivian , Rose Stephen , Walker Joanna , Shaw Nick

Background: Acid-labile subunit (ALS) deficiency inhibits ternary complex formation leading to primary IGF1 deficiency and short stature. Potential metabolic consequences such as diabetes and low bone mass are not well studied.Objective: This study measured insulin sensitivity, lipid profile, bone density and structure in members of 4 affected families and explore possible gene-dose effects.Methods: Four patients (7–21 years) ...

ea0013p132 | Growth and development | SFEBES2007

An intronic growth hormone receptor mutation causing activation of a pseudoexon is associated with a broad spectrum of growth hormone insensitivity phenotypes

David Alessia , Camacho-Hubner Cecilia , Bhangoo Amrit , Rose Stephen , Miraki-Moud Farideh , Akker Scott , Butler Gary , Ten Svetlana , Clayton Peter , Clark Adrian , Savage Martin , Metherell Lou

Inherited growth hormone insensitivity (GHI) is usually caused by mutations in the GH receptor (GHR). Patients present with short stature associated with a mid-facial hypoplasia (Laron facial features) or with normal facial appearance. We previously described an intronic mutation in the GHR gene (A−1 to G−1 substitution in intron 6) resulting in the activation of a pseudoexon (6Ψ) in four related GHI patients with normal facial fea...

ea0058oc5.8 | Oral Communications 5 | BSPED2018

Patients with short stature and GH/IGF-1 insensitivity harbour copy number variants causing a Silver-Russell-like phenotype

Cottrell Emily , Chatterjee Sumana , Moore Gudrun , Ishida Miho , Greening James , Wright Neil , Bossowski Artur , Deeb Asma , Al Basiri Iman , Rose Stephen , Mason Avril , Ahn JooWook , Bint Susan , Savage Martin O , Metherell Louise A , Storr Helen L

Introduction: Our Centre receives international referrals for genetic analysis of children with short stature (SS) and features of GH/IGF-1 insensitivity. Copy number variation (CNV) hasn’t previously been investigated in GH/IGF-1 insensitivity. We hypothesised CNVs contribute to the phenotype in our undiagnosed cohort.Experimental design/methodology: CGH was performed with oligonucleotide array using ~60,000 probes in 60 patients (38 M, mean age 7....