{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T16:57:04Z","timestamp":1773421024824,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,6,9]],"date-time":"2016-06-09T00:00:00Z","timestamp":1465430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2016,10]]},"abstract":"Summary<\/jats:title>Objectives<\/jats:title>IGSF1 deficiency syndrome (IDS<\/jats:styled-content>) is a recently described X\u2010linked congenital central hypothyroidism disorder characterized by loss\u2010of\u2010function mutations in the immunoglobulin superfamily member 1 (IGSF<\/jats:styled-content>1)<\/jats:italic> gene. The phenotypic spectrum and intrafamilial variability associated with IDS<\/jats:styled-content> remain unclear due to a paucity of large, well\u2010characterized pedigrees. Here, we present phenotypic analysis and molecular characterization of a five\u2010generation pedigree with IGSF<\/jats:styled-content>1 deficiency containing 10 affected males.<\/jats:p><\/jats:sec>Patients and methods<\/jats:title>Pituitary function was assessed in all available family members (n<\/jats:italic> = 8 affected males and n<\/jats:italic> = 5 carrier females). Molecular characterization of the family was performed by Sanger sequencing of PCR<\/jats:styled-content> products amplified from the IGSF<\/jats:styled-content>1<\/jats:italic> locus and by array comparative genomic hybridization.<\/jats:p><\/jats:sec>Results<\/jats:title>A 42\u2010kb IGSF<\/jats:styled-content>1<\/jats:italic> deletion spanning the entire coding sequence was identified in all affected males. TSH<\/jats:styled-content> deficiency, although subclinical in one case, was identified in all affected males (n<\/jats:italic> = 8). PRL<\/jats:styled-content> and GH<\/jats:styled-content> deficiency were also present in 5 of 6 and 4 of 8 affected males, respectively. In contrast to previous reports, macroorchidism was not detected in any of the four affected males who were examined for this feature. Only 1 of 5 carrier females had pituitary dysfunction (TSH<\/jats:styled-content> and GH<\/jats:styled-content> deficiency).<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Individuals with identical IGSF<\/jats:styled-content>1<\/jats:italic> deletions can exhibit variable pituitary hormone deficiencies, of which overt TSH<\/jats:styled-content> deficiency is the most consistent feature. We also show that macroorchidism is not obligatory in males with IDS<\/jats:styled-content>. Mutations of IGSF<\/jats:styled-content>1<\/jats:italic> should therefore be considered in males with isolated hypopituitarism that includes TSH<\/jats:styled-content> deficiency.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.13094","type":"journal-article","created":{"date-parts":[[2016,5,5]],"date-time":"2016-05-05T07:53:01Z","timestamp":1462434781000},"page":"609-615","source":"Crossref","is-referenced-by-count":29,"title":["Identification of an IGSF1<\/i>\u2010specific deletion in a five\u2010generation pedigree with X\u2010linked Central Hypothyroidism without macroorchidism"],"prefix":"10.1111","volume":"85","author":[{"given":"James N.","family":"Hughes","sequence":"first","affiliation":[{"name":"School of Biological Sciences University of Adelaide Adelaide SA Australia"},{"name":"Robinson Research Institute University of Adelaide Adelaide SA Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Aubert","sequence":"additional","affiliation":[{"name":"School of Biological Sciences University of Adelaide Adelaide SA Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Heatlie","sequence":"additional","affiliation":[{"name":"School of Biological Sciences University of Adelaide Adelaide SA Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison","family":"Gardner","sequence":"additional","affiliation":[{"name":"School of Pediatrics and Reproductive Health The University of Adelaide Adelaide SA Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jozef","family":"Gecz","sequence":"additional","affiliation":[{"name":"Robinson Research Institute University of Adelaide Adelaide SA Australia"},{"name":"School of Pediatrics and Reproductive Health The University of Adelaide Adelaide SA Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Morgan","sequence":"additional","affiliation":[{"name":"Novartis Institutes of Biomedical Research Biomarkers Division Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Belsky","sequence":"additional","affiliation":[{"name":"Department of Medicine (Endocrinology) Yale University School of Medicine New Haven CT USA"},{"name":"Department of Medicine Danbury Hospital Danbury CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul Q.","family":"Thomas","sequence":"additional","affiliation":[{"name":"School of Biological Sciences University of Adelaide Adelaide SA Australia"},{"name":"Robinson Research Institute University of Adelaide Adelaide SA 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