{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T14:43:04Z","timestamp":1791211384245,"version":"4.1.0"},"reference-count":9,"publisher":"The Endocrine Society","issue":"3","license":[{"start":{"date-parts":[[2020,11,29]],"date-time":"2020-11-29T00:00:00Z","timestamp":1606608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K16164"],"award-info":[{"award-number":["17K16164"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23659477"],"award-info":[{"award-number":["23659477"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["26670459"],"award-info":[{"award-number":["26670459"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["17bm0804012h0001"],"award-info":[{"award-number":["17bm0804012h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008732","name":"Uehara Memorial Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008732","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007428","name":"Naito Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Luscan-Lumish syndrome (LLS) is characterized by postnatal overgrowth, obesity, Chiari I malformation, seizures, and intellectual disability. SET domain-containing protein 2 (SETD2) is a histone methyltransferase, where mutations in the gene are associated with the development of LLS. However, mechanisms underlying LLS remain unclear.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Case Description<\/jats:title>\n                  <jats:p>A 20-year-old man was referred to our hospital because of tall stature. His body height was 188.2 cm (+3.18 SD) and he showed obesity with a body mass index of 28.4 kg\/m2. He exhibited acral overgrowth, jaw malocclusion, and prognathism, but no history of seizures, intellectual disability, or speech delay. Serum growth hormone (GH), insulin-like growth factor 1 (IGF-1), and nadir GH levels after administration of 75 g oral glucose were within normal range. Pituitary magnetic resonance imaging showed no pituitary adenoma, but Chiari I malformation. Whole exome sequencing analysis of the proband revealed a de novo heterozygous germline mutation in SETD2 (c.236T&amp;gt;A, p.L79H). Skin fibroblasts derived from the patient grew faster than those from his father and the control subject. In addition, these cells showed enhanced tyrosine phosphorylation and transcriptional activity of signal transducer and activator of transcription 5b (STAT5b) and increased IGF-1 expression induced by GH.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>This is a mild case of LLS with a novel mutation in SETD2 without neurological symptoms. LLS should be differentiated in a patient with gigantism without pituitary tumors. Although further investigation is necessary, this is the first study to suggest the involvement of aberrant GH signaling in the development of LLS.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa893","type":"journal-article","created":{"date-parts":[[2020,11,29]],"date-time":"2020-11-29T00:36:46Z","timestamp":1606610206000},"page":"718-723","source":"Crossref","is-referenced-by-count":9,"title":["A Case of Luscan-Lumish Syndrome: Possible Involvement of Enhanced GH Signaling"],"prefix":"10.1210","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6734-5183","authenticated-orcid":false,"given":"Kentaro","family":"Suda","sequence":"first","affiliation":[{"name":"Division of Diabetes and Endocrinology, Kobe University Hospital, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9255-653X","authenticated-orcid":false,"given":"Hidenori","family":"Fukuoka","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Kobe University Hospital, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genzo","family":"Iguchi","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Kobe University Hospital, Kobe, Japan"},{"name":"Medical Center for Student Health, Kobe University, Kobe, Japan"},{"name":"Department of Biosignal Pathophysiology, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keitaro","family":"Kanie","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunori","family":"Fujita","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Odake","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryusaku","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironori","family":"Bando","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Ito","sequence":"additional","affiliation":[{"name":"Center for Medical Education and Training, Shonan Fujisawa Tokushukai Hospital, Fujisawa, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiko","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Kobe University Hospital, Kobe, Japan"},{"name":"Department of Nutrition, Kobe University Hospital, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Chihara","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology, Akashi Medical Center, Akashi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Nagai","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0940-4517","authenticated-orcid":false,"given":"Satoshi","family":"Narumi","sequence":"additional","affiliation":[{"name":"Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan"},{"name":"Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0143-3989","authenticated-orcid":false,"given":"Tomonobu","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1337-9246","authenticated-orcid":false,"given":"Yutaka","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan"},{"name":"Department of Diabetes and Endocrinology, Nara Medical University, Kashihara, Nara, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2020,11,29]]},"reference":[{"issue":"2","key":"2021122117352639000_CIT0001","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1159\/000484532","article-title":"A clinical review of generalized overgrowth syndromes in the era of massively parallel sequencing","volume":"9","author":"Kamien","year":"2018","journal-title":"Mol Syndromol."},{"issue":"11","key":"2021122117352639000_CIT0002","doi-asserted-by":"crossref","first-page":"3764","DOI":"10.1007\/s10803-015-2484-8","article-title":"Brief report: SETD2 mutation in a child with autism, intellectual disabilities and epilepsy","volume":"45","author":"Lumish","year":"2015","journal-title":"J Autism Dev Disord."},{"issue":"2","key":"2021122117352639000_CIT0003","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/nrm3274","article-title":"Understanding the language of Lys36 methylation at histone H3","volume":"13","author":"Wagner","year":"2012","journal-title":"Nat Rev Mol Cell Biol."},{"issue":"7","key":"2021122117352639000_CIT0004","doi-asserted-by":"crossref","first-page":"2956","DOI":"10.1073\/pnas.0915033107","article-title":"Histone H3 lysine 36 methyltransferase Hypb\/Setd2 is required for embryonic vascular remodeling","volume":"107","author":"Hu","year":"2010","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"1","key":"2021122117352639000_CIT0005","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1096\/fj.201901757R","article-title":"DNA methylation analysis of multiple imprinted DMRs in Sotos syndrome reveals IGF2-DMR0 as a DNA methylation-dependent, P0 promoter-specific enhancer","volume":"34","author":"Watanabe","year":"2020","journal-title":"Faseb J."},{"issue":"18","key":"2021122117352639000_CIT0006","doi-asserted-by":"crossref","first-page":"8774","DOI":"10.1093\/nar\/gkv776","article-title":"Loss of EZH2 results in precocious mammary gland development and activation of STAT5-dependent genes","volume":"43","author":"Yoo","year":"2015","journal-title":"Nucleic Acids Res."},{"issue":"16","key":"2021122117352639000_CIT0007","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res."},{"issue":"9","key":"2021122117352639000_CIT0008","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1093\/hmg\/7.9.1463","article-title":"Huntingtin interacts with a family of WW domain proteins","volume":"7","author":"Faber","year":"1998","journal-title":"Hum Mol Genet."},{"issue":"6790","key":"2021122117352639000_CIT0009","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1038\/35016611","article-title":"Gigantism in mice lacking suppressor of cytokine signalling-2","volume":"405","author":"Metcalf","year":"2000","journal-title":"Nature."}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgaa893\/36150431\/dgaa893.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/106\/3\/718\/41832982\/dgaa893.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/106\/3\/718\/41832982\/dgaa893.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T18:06:50Z","timestamp":1640110010000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/106\/3\/718\/6009067"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,29]]},"references-count":9,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,11,29]]},"published-print":{"date-parts":[[2021,3,8]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgaa893","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,3,1]]},"published":{"date-parts":[[2020,11,29]]}}}