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In addition to these symptoms patients with Hartsfield syndrome can show developmental delay of variable severity, isolated hypogonadotropic hypogonadism, central diabetes insipidus, vertebral anomalies, eye anomalies, and cardiac malformations. Pathogenic variants in <jats:italic>FGFR1<\/jats:italic> have been described to cause phenotypically different <jats:italic>FGFR1<\/jats:italic>\u2010related disorders such as Hartsfield syndrome, hypogonadotropic hypogonadism with or without anosmia, Jackson\u2013Weiss syndrome, osteoglophonic dysplasia, Pfeiffer syndrome, and trigonocephaly Type 1. Here, we report three patients with Hartsfield syndrome from two unrelated families. Exome sequencing revealed two siblings harboring a novel <jats:italic>de novo<\/jats:italic> heterozygous synonymous variant c.1029G&gt;A, p.Ala343Ala causing a cryptic splice donor site in exon 8 of <jats:italic>FGFR1<\/jats:italic> likely due to gonadal mosaicism in one parent. The third case was a sporadic patient with a novel <jats:italic>de novo<\/jats:italic> heterozygous missense variant c.1868A&gt;G, p.(Asp623Gly).<\/jats:p>","DOI":"10.1002\/ajmg.a.61354","type":"journal-article","created":{"date-parts":[[2019,9,12]],"date-time":"2019-09-12T06:58:56Z","timestamp":1568271536000},"page":"2447-2453","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Novel synonymous and missense variants in FGFR1 causing Hartsfield syndrome"],"prefix":"10.1002","volume":"179","author":[{"given":"Carolina","family":"Courage","sequence":"first","affiliation":[{"name":"Folkh\u00e4lsan Research Center  Helsinki Finland"},{"name":"Division of Human Genetics, Department of Pediatrics, Inselspital University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1035-6417","authenticated-orcid":false,"given":"Christopher B.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Stem Cells and Metabolism Research Program, Faculty of Medicine University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Owczarek\u2010Lipska","sequence":"additional","affiliation":[{"name":"Human Genetics, Faculty of Medicine and Health Sciences University of Oldenburg  Oldenburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksander","family":"Jamsheer","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Poznan University of Medical Sciences  Poznan Poland"},{"name":"Centers for Medical Genetics GENESIS  Poznan Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Sowi\u0144ska\u2010Seidler","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Poznan University of Medical Sciences  Poznan Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Piotrowicz","sequence":"additional","affiliation":[{"name":"Department of Genetics Polish Mother's Memorial Hospital Research Institute  Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucjusz","family":"Jakubowski","sequence":"additional","affiliation":[{"name":"Department of Genetics Polish Mother's Memorial Hospital Research Institute  Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny","family":"Dall\u00e8ves","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Pediatrics, Inselspital University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Riesch","sequence":"additional","affiliation":[{"name":"CeGaT GmbH\u2014Center for Genomics and Transcriptomics  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Neidhardt","sequence":"additional","affiliation":[{"name":"Human Genetics, Faculty of Medicine and Health Sciences University of Oldenburg  Oldenburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes R.","family":"Lemke","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Leipzig Medical Center  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,9,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.02.006"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36621"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1122"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23038"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2015.03.003"},{"key":"e_1_2_9_7_1","first-page":"27","article-title":"Hypertelorism associated with holoprosencephaly and ectrodactyly","volume":"12","author":"Hartsfield J. 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