Abstract Search

hrp0095fc10.6 | GH and IGFs | ESPE2022

Defects in QSOX2, a novel regulator of STAT5B nuclear import and transcriptional activity, lead to severe post-natal growth restriction

Maharaj Avinaash , Andrews Afiya , Chatterjee Sumana , Hwa Vivian , Storr Helen

Background: Growth Hormone Insensitivity (GHI) is characterised by short stature and functional IGF-I deficiency associated with normal/elevated GH levels. Marked genetic and phenotypic heterogeneity exist, and heritable defects in GH-IGF-I axis genes/associated pathways account for mild-moderate to severe GHI cases. We report twin brothers from a non-consanguineous kindred who present with short stature and bi-allelic mutations in QSOX2 encoding the nuclear m...

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hrp0098ha2 | A novel human disorder: QSOX2 deficiency‐induced growth restriction, gastrointestinal dysmotility and immune dysfunction highlights a new mechanism of disease. | ESPE2024

A novel human disorder: QSOX2 deficiency-induced growth restriction, gastrointestinal dysmotility and immune dysfunction highlights a new mechanism of disease.

Maharaj Avinaash , Ishida Miho , Rybak Anna , Elfeky Reem , Andrews Afiya , McGuffin Liam , Hwa Vivian , Storr Helen

Background: Defects in growth hormone (GH) action account for a substantial percentage of endocrine causes of growth restriction but are frequently unrecognised due to wide clinical and biochemical variability. We report five probands from three families who present with short stature, features of atypical growth hormone insensitivity (GHI), immune dysfunction, atopic eczema, and gastrointestinal pathology associated with novel recessive variants in a new gene...

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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...

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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...

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ePoster

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...

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ESPE Abstracts

Defects in QSOX2, a novel regulator of STAT5B nuclear import and transcriptional activity, lead to severe post-natal growth restriction

A novel human disorder: QSOX2 deficiency-induced growth restriction, gastrointestinal dysmotility and immune dysfunction highlights a new mechanism of disease.

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

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

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

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