{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T14:21:15Z","timestamp":1785766875708,"version":"3.56.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"6","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>Copy number variation (CNV) has been associated with idiopathic short stature, small for gestational age and Silver-Russell syndrome (SRS). It has not been extensively investigated in growth hormone insensitivity (GHI; short stature, IGF-1 deficiency and normal\/high GH) or previously in IGF-1 insensitivity (short stature, high\/normal GH and IGF-1).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Design and methods<\/jats:title>\n<jats:p>Array comparative genomic hybridisation was performed with ~60 000 probe oligonucleotide array in GHI (<jats:italic>n<\/jats:italic> = 53) and IGF-1 insensitivity (<jats:italic>n<\/jats:italic> = 10) subjects. Published literature, mouse models, DECIPHER CNV tracks, growth associated GWAS loci and pathway enrichment analyses were used to identify key biological pathways\/novel candidate growth genes within the CNV regions.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Both cohorts were enriched for class 3\u20135 CNVs (7\/53 (13%) GHI and 3\/10 (30%) IGF-1 insensitivity patients). Interestingly, 6\/10 (60%) CNV subjects had diagnostic\/associated clinical features of SRS. 5\/10 subjects (50%) had CNVs previously reported in suspected SRS: 1q21 (<jats:italic>n<\/jats:italic> = 2), 12q14 (<jats:italic>n<\/jats:italic> = 1) deletions and Xp22 (<jats:italic>n<\/jats:italic> = 1), Xq26 (<jats:italic>n<\/jats:italic> = 1) duplications. A novel 15q11 deletion, previously associated with growth failure but not SRS\/GHI was identified. Bioinformatic analysis identified 45 novel candidate growth genes, 15 being associated with growth in GWAS. The WNT canonical pathway was enriched in the GHI cohort and <jats:italic>CLOCK<\/jats:italic> was identified as an upstream regulator in the IGF-1 insensitivity cohorts.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Our cohort was enriched for low frequency CNVs. Our study emphasises the importance of CNV testing in GHI and IGF-1 insensitivity patients, particularly GHI subjects with SRS features. Functional experimental evidence is now required to validate the novel candidate growth genes, interactions and biological pathways identified.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-20-0474","type":"journal-article","created":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T15:55:42Z","timestamp":1600358142000},"page":"581-595","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":7,"title":["Rare CNVs provide novel insights into the molecular basis of GH and IGF-1 insensitivity"],"prefix":"10.1093","volume":"183","author":[{"given":"Emily","family":"Cottrell","sequence":"first","affiliation":[{"name":"1Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia P","family":"Cabrera","sequence":"additional","affiliation":[{"name":"2Centre for Translational Bioinformatics, Queen Mary University of London, London, UK"},{"name":"3NIHR Barts Cardiovascular Biomedical Research Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miho","family":"Ishida","sequence":"additional","affiliation":[{"name":"4University College London, Great Ormond Street Institute of Child Health, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumana","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"1Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Greening","sequence":"additional","affiliation":[{"name":"5University Hospitals of Leicester NHS Trust, Leicester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Wright","sequence":"additional","affiliation":[{"name":"6The University of Sheffield Faculty of Medicine, Dentistry and Health, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artur","family":"Bossowski","sequence":"additional","affiliation":[{"name":"7Department of Pediatrics, Endocrinology and Diabetes with a Cardiology Unit, Medical University of Bialystok, Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Dunkel","sequence":"additional","affiliation":[{"name":"1Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma","family":"Deeb","sequence":"additional","affiliation":[{"name":"8Paediatric Endocrinology Department, Mafraq Hospital, Abu Dhabi, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iman Al","family":"Basiri","sequence":"additional","affiliation":[{"name":"9Mubarak Al-kabeer Hospital, Jabriya, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J","family":"Rose","sequence":"additional","affiliation":[{"name":"10University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avril","family":"Mason","sequence":"additional","affiliation":[{"name":"11Royal Hospital for Children, Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Bint","sequence":"additional","affiliation":[{"name":"12Viapath, Guy\u2019s Hospital, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo Wook","family":"Ahn","sequence":"additional","affiliation":[{"name":"13Addenbrookes Hospital, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian","family":"Hwa","sequence":"additional","affiliation":[{"name":"14Cincinnati Center for Growth Disorders, Division of Endocrinology, Cincinnati Children\u2019s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise A","family":"Metherell","sequence":"additional","affiliation":[{"name":"1Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gudrun E","family":"Moore","sequence":"additional","affiliation":[{"name":"4University College London, Great Ormond Street Institute of Child Health, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen L","family":"Storr","sequence":"additional","affiliation":[{"name":"1Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/183\/6\/EJE-20-0474.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/downloadpdf\/journals\/eje\/183\/6\/EJE-20-0474.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:15:06Z","timestamp":1676391306000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/183\/6\/581\/6653841"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12]]},"references-count":0,"journal-issue":{"issue":"6"},"URL":"https:\/\/doi.org\/10.1530\/eje-20-0474","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12]]}}}