{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:53:00Z","timestamp":1753890780039,"version":"3.41.2"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T00:00:00Z","timestamp":1646006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p><jats:italic>SOX3<\/jats:italic> is critical for the development of the pituitary, brain, and face, and <jats:italic>SOX3<\/jats:italic> mutations may lead to hypopituitarism, intellectual disability, and craniofacial abnormalities. Common <jats:italic>SOX3<\/jats:italic> mutations are duplications and deletions of the whole or part of <jats:italic>SOX3<\/jats:italic>, yet only a few cases with point mutations were reported by far. We present a case with growth retardation, small penis, and learning difficulty. Further assessment confirmed growth hormone deficiency, hypogonadotropic hypogonadism (HH), and borderline intellectual disability. He also responded well to gonadotropin-releasing hormone stimulation test, which suggests defects in the hypothalamus, contrary to previous studies that reported defects in the pituitary. A pathogenic frame-shift mutation of <jats:italic>SOX3<\/jats:italic> was found. A heterogeneous missense mutation in <jats:italic>SEMA3A<\/jats:italic> was identified in this patient as well, which may also contribute to the development of HH. As far as we know, this is the first report that a frame-shift mutation of <jats:italic>SOX3<\/jats:italic> constitutes rare genetic causes of HH and growth hormone deficiency. Whether mutations in these two genes act synergistically in the pathogenesis of the patient\u2019s phenotype remains to be further investigated. We believe that our case extends the phenotypic spectrum and genetic variability of <jats:italic>SOX3<\/jats:italic> mutation.<\/jats:p>","DOI":"10.3389\/fendo.2022.810375","type":"journal-article","created":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T05:02:19Z","timestamp":1646024539000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Case Report: A Novel Point Mutation of SOX3 in a Subject With Growth Hormone Deficiency, Hypogonadotrophic Hypogonadism, and Borderline Intellectual Disability"],"prefix":"10.3389","volume":"13","author":[{"given":"Jing","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxia","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yerong","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianwei","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/2.12.2013","article-title":"SOX3 is an X-Linked Gene Related to SRY","volume":"2","author":"Stevanovl\u0107","year":"1993","journal-title":"Hum Mol Genet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.122.2.509","article-title":"A Comparison of the Properties of Sox-3 With Sry and Two Related Genes, Sox-1 and Sox-2","volume":"122","author":"Collignon","year":"1996","journal-title":"Development"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-020-01101-8","article-title":"Congenital Hypopituitarism in Two Brothers With a Duplication of the 'Acrogigantism Gene' GPR101: Clinical Findings and Review of the Literature","volume":"24","author":"Elizabeth","year":"2021","journal-title":"Pituitary"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/ng1309","article-title":"SOX3 is Required During the Formation of the Hypothalamo-Pituitary Axis","volume":"36","author":"Rizzoti","year":"2004","journal-title":"Nat Genet"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1097\/MCD.0b013e32832d06f0","article-title":"X-Linked Isolated Growth Hormone Deficiency: Expanding the Phenotypic Spectrum of SOX3 Polyalanine Tract Expansions","volume":"18","author":"Burkitt Wright","year":"2009","journal-title":"Clin Dysmorphol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1159\/000503784","article-title":"Xq27.1 Duplication Encompassing SOX3: Variable Phenotype and Smallest Duplication Associated With Hypopituitarism to Date - 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