{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T04:09:35Z","timestamp":1791691775122,"version":"4.3.4"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T00:00:00Z","timestamp":1710115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014252","name":"Fondo Argentino Sectorial","doi-asserted-by":"publisher","award":["FS-BIO 05\/2017 Cat.III 73\/2021"],"award-info":[{"award-number":["FS-BIO 05\/2017 Cat.III 73\/2021"]}],"id":[{"id":"10.13039\/501100014252","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Pubertal delay can be due to hypogonadotropic hypogonadism (HH), which may occur in association with anosmia or hyposmia and is known as Kallmann syndrome (OMIM #308700). Recently, hypogonadotropic hypogonadism has been suggested to overlap with Witteveen\u2013Kolk syndrome (WITKOS, OMIM #613406) associated with 15q24 microdeletions encompassing <jats:italic>SIN3A<\/jats:italic>. Whether hypogonadotropic hypogonadism is due to haploinsufficiency of <jats:italic>SIN3A<\/jats:italic> or any of the other eight genes present in 15q24 is not known. We report the case of a female patient with delayed puberty associated with intellectual disability, behavior problems, dysmorphic facial features, and short stature, at the age of 14\u00a0years. Clinical, laboratory, and imaging assessments confirmed the diagnosis of Kallmann syndrome. Whole-exome sequencing identified a novel heterozygous frameshift variant, NM_001145358.2:c.3045_3046dup, NP_001138830.1:p.(Ile1016Argfs*6) in <jats:italic>SIN3A<\/jats:italic>, classified as pathogenic according to the American College of Medical Genetics and Genomics (ACMG\/AMP) criteria. Reverse phenotyping led to the clinical diagnosis of WITKOS. No other variant was found in the 96 genes potentially related to hypogonadotropic hypogonadism. The analysis of the other contiguous seven genes to <jats:italic>SIN3A<\/jats:italic> in 15q24 did not reveal any clinically relevant variant. In conclusion, these findings point to <jats:italic>SIN3A<\/jats:italic> as the gene in 15q24 related to the reproductive phenotype in patients with overlapping WITKOS and Kallmann syndrome.<\/jats:p>","DOI":"10.3389\/fgene.2024.1354715","type":"journal-article","created":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T04:58:49Z","timestamp":1710133129000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Case report: Novel SIN3A loss-of-function variant as causative for hypogonadotropic hypogonadism in Witteveen\u2013Kolk syndrome"],"prefix":"10.3389","volume":"15","author":[{"given":"Lourdes","family":"Correa Brito","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Keselman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florencia","family":"Villegas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Scaglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Esnaola Azcoiti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebasti\u00e1n","family":"Castro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Sanguineti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agust\u00edn","family":"Izquierdo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianela","family":"Maier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Bergad\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Arberas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodolfo A.","family":"Rey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Gabriela","family":"Ropelato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,3,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1038\/s41431-020-00769-7","article-title":"Comprehensive study of 28 individuals with SIN3A-related disorder underscoring the associated mild cognitive and distinctive facial phenotype","volume":"29","author":"Balasubramanian","year":"2021","journal-title":"Eur. 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