{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T13:54:27Z","timestamp":1753883667775,"version":"3.41.2"},"reference-count":24,"publisher":"The Endocrine Society","issue":"5","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015652","name":"Barts Charity","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015652","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The main features of immunoglobulin superfamily, member 1 (IGSF1) deficiency are central hypothyroidism and macroorchidism. The phenotype can be variable and may include macrosomia, hypoprolactinemia, growth hormone (GH) secretory abnormalities, delayed puberty, and obesity. We describe a novel de novo nonsense pathogenic variant c.3343C &amp;gt; T, p.(Gln1115*) that localizes to the 12th and last immunoglobulin-like loop in the C-terminal domain of the protein. The patient was born in breech with a birth weight of 3.7\u2005kg. At presentation aged 15 years, he had obesity, central hypothyroidism, reduced attention, macroorchidism with delayed adrenarche and pubertal development. There was evidence of transient biochemical GH deficiency with normoprolactinemia and a small pituitary on magnetic resonance imaging, although interpretation of dynamic GH testing was difficult due to poor adherence with levothyroxine. He continued growing without GH treatment, and after spontaneous puberty, insulin-like growth factor-1 concentration was high. At age 22 years, he was 190\u2005cm (+1.9 SDS), 155.4\u2005kg (body mass index 43.05), with 35\u2005mL testes. The transient GH deficiency and normoprolactinemia support a role for IGSF1 in somatotroph function.<\/jats:p>","DOI":"10.1210\/jcemcr\/luaf033","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T10:26:46Z","timestamp":1744367206000},"source":"Crossref","is-referenced-by-count":0,"title":["A Novel De Novo Nonsense Pathogenic Variant in <i>IGSF1<\/i> Resulting in Central Hypothyroidism and Transient GH Deficiency"],"prefix":"10.1210","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0744-5275","authenticated-orcid":false,"given":"James","family":"Blackburn","sequence":"first","affiliation":[{"name":"Department of Paediatric Endocrinology and Diabetes, Barts Health NHS Trust, Royal London Hospital , Whitechapel, London E1 1BB ,","place":["UK"]},{"name":"Centre for Endocrinology, Queen Mary University of London , London EC1M 6BQ ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Banupriya","family":"Sivasanker","sequence":"additional","affiliation":[{"name":"Department of Paediatric Endocrinology and Diabetes, Barts Health NHS Trust, Royal London Hospital , Whitechapel, London E1 1BB ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahida","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Basildon University Hospital, Mid and South Essex NHS Foundation Trust , Nethermayne, Basildon, Essex SS16 5NL ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birgit","family":"van Meijgaarden","sequence":"additional","affiliation":[{"name":"Basildon University Hospital, Mid and South Essex NHS Foundation Trust , Nethermayne, Basildon, Essex SS16 5NL ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4101-9432","authenticated-orcid":false,"given":"Marta","family":"Korbonits","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, Queen Mary University of London , London EC1M 6BQ ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4397-4126","authenticated-orcid":false,"given":"Evelien","family":"Gevers","sequence":"additional","affiliation":[{"name":"Department of Paediatric Endocrinology and Diabetes, Barts Health NHS Trust, Royal London Hospital , Whitechapel, London E1 1BB ,","place":["UK"]},{"name":"Centre for Endocrinology, Queen Mary University of London , London EC1M 6BQ 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children with central congenital hypothyroidism, early detected by neonatal screening","volume":"183","author":"Naafs","year":"2020","journal-title":"Eur J Endocrinol"},{"issue":"12","key":"2025041110173875900_luaf033-B4","doi-asserted-by":"crossref","first-page":"6229","DOI":"10.1210\/jc.2019-00657","article-title":"Genetics of congenital isolated TSH deficiency: mutation screening of the known causative genes and a literature review","volume":"104","author":"Sugisawa","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"2025041110173875900_luaf033-B5","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1111\/cen.13827","article-title":"A novel IGSF1 mutation in a large Irish kindred highlights the need for familial screening in the IGSF1 deficiency syndrome","volume":"89","author":"Roche","year":"2018","journal-title":"Clin Endocrinol 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