{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T18:54:58Z","timestamp":1792695298983,"version":"4.5.0"},"reference-count":32,"publisher":"The Endocrine Society","issue":"5","license":[{"start":{"date-parts":[[2020,4,3]],"date-time":"2020-04-03T00:00:00Z","timestamp":1585872000000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Hartsfield syndrome (HS: OMIM 615465) is a rare congenital disease associated with a mutation of the fibroblast growth factor receptor 1 gene (FGFR1) with the main features of holoprosencephaly and ectrodactyly. Patients with HS also present with endocrinological deficits, such as isolated hypogonadotropic hypogonadism and central diabetes insipidus. Although there are several studies on infancy\/childhood history, there is no study of infant\/childhood\/adolescent\/young adult HS natural history and endocrinological findings. Here, we report a male patient with HS associated with a novel de novo FGFR1 mutation (c. 1868A\u2005&amp;gt;\u2005C). The endocrinological profile was evaluated at ages 1 and 31 years. This long-term follow-up study highlights functional changes in the posterior pituitary gland and features of bone metabolism disorder. We also describe the anterior pituitary function. To our knowledge this is the first description of the natural history of an HS patient through birth to young adult age. Although the HS infants reported in the literature develop central diabetes insipidus, little is known about the serial changes in pituitary gland function during growth in HS patients. In this study we describe an adult patient with HS who showed improvement of hypernatremia during early adulthood. In addition, we emphasize the importance of prevention and treatment of osteoporosis in HS.<\/jats:p>","DOI":"10.1210\/jendso\/bvaa041","type":"journal-article","created":{"date-parts":[[2020,4,3]],"date-time":"2020-04-03T18:05:27Z","timestamp":1585937127000},"source":"Crossref","is-referenced-by-count":3,"title":["Endocrinological Features of Hartsfield Syndrome in an Adult Patient With a Novel Mutation of <i>FGFR1<\/i>"],"prefix":"10.1210","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4359-0381","authenticated-orcid":false,"given":"Sachiko","family":"Kobayashi","sequence":"first","affiliation":[{"name":"Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Yamadaoka, Suita, Osaka, Japan"},{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Daini Osaka Police Hospital, Karasugatsuji, Ten-noji, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junpei","family":"Tanigawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine, Osaka University, Yamadaoka, Suita, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidehito","family":"Kondo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine, Osaka University, Yamadaoka, Suita, Osaka, Japan"},{"name":"Department of Pediatrics, Kyoto Daiichi Red Cross Hospital, Honmachi, Higashiyama-ku, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8453-2028","authenticated-orcid":false,"given":"Shin","family":"Nabatame","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine, Osaka University, Yamadaoka, Suita, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azusa","family":"Maruoka","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Daini Osaka Police Hospital, Karasugatsuji, Ten-noji, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Sho","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Daini Osaka Police Hospital, Karasugatsuji, Ten-noji, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuko","family":"Tanikawa","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Daini Osaka Police Hospital, Karasugatsuji, Ten-noji, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoko","family":"Inui","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Daini Osaka Police Hospital, Karasugatsuji, Ten-noji, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5947-8621","authenticated-orcid":false,"given":"Michio","family":"Otsuki","sequence":"additional","affiliation":[{"name":"Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Yamadaoka, Suita, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iichiro","family":"Shimomura","sequence":"additional","affiliation":[{"name":"Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Yamadaoka, Suita, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichi","family":"Ozono","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine, Osaka University, Yamadaoka, Suita, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunihiko","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Daini Osaka Police Hospital, Karasugatsuji, Ten-noji, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2020,4,2]]},"reference":[{"issue":"9","key":"2021121116405788100_CIT0001","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1136\/jmedgenet-2013-101603","article-title":"FGFR1 mutations cause Hartsfield syndrome, the unique association of holoprosencephaly and ectrodactyly","volume":"50","author":"Simonis","year":"2013","journal-title":"J Med Genet."},{"issue":"9","key":"2021121116405788100_CIT0002","doi-asserted-by":"crossref","first-page":"2356","DOI":"10.1002\/ajmg.a.36621","article-title":"Novel de novo heterozygous FGFR1 mutation in two siblings with Hartsfield syndrome: a case of gonadal mosaicism","volume":"164A","author":"Dhamija","year":"2014","journal-title":"Am J Med Genet A."},{"issue":"10","key":"2021121116405788100_CIT0003","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1093\/hmg\/ddw064","article-title":"Dominant-negative kinase domain mutations in FGFR1 can explain the clinical severity of Hartsfield syndrome","volume":"25","author":"Hong","year":"2016","journal-title":"Hum Mol Genet."},{"issue":"8","key":"2021121116405788100_CIT0004","doi-asserted-by":"crossref","first-page":"2222","DOI":"10.1002\/ajmg.a.37731","article-title":"Hartsfield syndrome associated with a novel heterozygous missense mutation in FGFR1 and incorporating tumoral calcinosis","volume":"170","author":"Prasad","year":"2016","journal-title":"Am J Med Genet A."},{"key":"2021121116405788100_CIT0005","doi-asserted-by":"crossref","first-page":"16034","DOI":"10.1038\/hgv.2016.34","article-title":"Novel heterozygous mutation in the extracellular domain of FGFR1 associated with Hartsfield syndrome","volume":"3","author":"Takagi","year":"2016","journal-title":"Hum Genome Var."},{"issue":"12","key":"2021121116405788100_CIT0006","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1002\/humu.23038","article-title":"Mutational spectrum in holoprosencephaly shows that FGF is a new major signaling pathway","volume":"37","author":"Dubourg","year":"2016","journal-title":"Hum Mutat."},{"issue":"11","key":"2021121116405788100_CIT0007","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1177\/0022034517726496","article-title":"The use of variant maps to explore domain-specific mutations of FGFR1","volume":"96","author":"Lansdon","year":"2017","journal-title":"J Dent Res."},{"issue":"7","key":"2021121116405788100_CIT0008","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1038\/s41431-019-0350-4","article-title":"A novel dominant-negative FGFR1 variant causes Hartsfield syndrome by deregulating RAS\/ERK1\/2 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(Oxf)."},{"issue":"9","key":"2021121116405788100_CIT0012","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1172\/JCI107423","article-title":"Development and clinical application of a new method for the radioimmunoassay of arginine vasopressin in human plasma","volume":"52","author":"Robertson","year":"1973","journal-title":"J Clin Invest."},{"issue":"10","key":"2021121116405788100_CIT0013","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1007\/s00198-014-2794-2","article-title":"Clinician\u2019s guide to prevention and treatment of osteoporosis","volume":"25","author":"Cosman","year":"2014","journal-title":"Osteoporos Int."},{"issue":"1","key":"2021121116405788100_CIT0014","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1006\/dbio.1997.8553","article-title":"Fibroblast growth factor receptor-1 (FGFR-1) is essential for normal neural tube and limb development","volume":"185","author":"Deng","year":"1997","journal-title":"Dev 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Metab"}],"container-title":["Journal of the Endocrine Society"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jes\/advance-article-pdf\/doi\/10.1210\/jendso\/bvaa041\/32994998\/bvaa041.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jes\/article-pdf\/4\/5\/bvaa041\/41727147\/bvaa041.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jes\/article-pdf\/4\/5\/bvaa041\/41727147\/bvaa041.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,11]],"date-time":"2021-12-11T16:41:38Z","timestamp":1639240898000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jes\/article\/doi\/10.1210\/jendso\/bvaa041\/5815590"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,2]]},"references-count":32,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,5,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jendso\/bvaa041","relation":{},"ISSN":["2472-1972"],"issn-type":[{"value":"2472-1972","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,5]]},"published":{"date-parts":[[2020,4,2]]},"article-number":"bvaa041"}}