{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T11:18:50Z","timestamp":1764587930698,"version":"3.37.3"},"reference-count":29,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,7,16]],"date-time":"2018-07-16T00:00:00Z","timestamp":1531699200000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32GM007454"],"award-info":[{"award-number":["T32GM007454"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:p>Pathogenic variants in the fibroblast growth factor receptor 3 (<jats:italic>FGFR3<\/jats:italic>) gene are responsible for a broad spectrum of skeletal dysplasias, including achondroplasia (ACH). The classic phenotype of ACH is caused by two highly prevalent mutations, c.1138G\u2009&gt;\u2009A and c.1138G\u2009&gt;\u2009C (p.Gly380Arg). In the homozygous state, these variant results in a severe skeletal dysplasia, neurologic deficits, and early demise from respiratory insufficiency. Although homozygous biallelic mutations have been reported in patients with ACH in combination with hypochondroplasia or other dominant skeletal dysplasias, thus far, no cases of heterozygous biallelic pathogenic ACH\u2010related variants in<jats:italic>FGFR3<\/jats:italic>have been reported. We describe a novel phenotype of an infant with two ACH\u2010related mutations in<jats:italic>FGFR3<\/jats:italic>, p.Gly380Arg and p.Ser344Cys. Discordant features from classic ACH include atypical radiographic findings, severe obstructive sleep apnea, and focal, migrating seizures. We also report the long\u2010term clinical course of her father, who harbors the p.Ser344Cys mutation that has only been reported once previously in a Japanese patient. The phenotype of heterozygous biallelic mutations in<jats:italic>FGFR3<\/jats:italic>associated with ACH is variable, underscoring the importance of recognition and accurate diagnosis to ensure appropriate management.<\/jats:p>","DOI":"10.1002\/ajmg.a.38839","type":"journal-article","created":{"date-parts":[[2018,7,17]],"date-time":"2018-07-17T06:43:12Z","timestamp":1531809792000},"page":"1675-1679","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Novel phenotype of achondroplasia due to biallelic<i>FGFR3<\/i>pathogenic variants"],"prefix":"10.1002","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5842-5912","authenticated-orcid":false,"given":"Irene J.","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Medical Genetics University of Washington Medical Center Seattle Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8348-4474","authenticated-orcid":false,"given":"Angela","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Genetic Medicine Seattle Children's Hospital and University of Washington Seattle Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1321-2478","authenticated-orcid":false,"given":"Maryse L.","family":"Bouchard","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Sports Medicine Seattle Children's Hospital Seattle Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shawn E.","family":"Kamps","sequence":"additional","affiliation":[{"name":"Department of Radiology Seattle Children's Hospital Seattle Washington"},{"name":"Department of Radiology University of Washington Medical Center Seattle Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Hale","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Genetic Medicine Seattle Children's Hospital and University of Washington Seattle Washington"},{"name":"Department of Orthopedics and Sports Medicine Seattle Children's Hospital Seattle Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Done","sequence":"additional","affiliation":[{"name":"Department of Radiology Seattle Children's Hospital Seattle Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Goldberg","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Sports Medicine Seattle Children's Hospital Seattle Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian A.","family":"Glass","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University of Washington Medical Center Seattle Washington"},{"name":"Department of Pediatrics, Division of Genetic Medicine Seattle Children's Hospital and University of Washington Seattle Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,7,16]]},"reference":[{"issue":"2","key":"e_1_2_6_2_1","first-page":"368","article-title":"Achondroplasia is defined by recurrent G380R mutations of FGFR3","volume":"56","author":"Bellus G. A.","year":"1995","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19960503)63:1<148::AID-AJMG26>3.0.CO;2-N"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19990611)84:5<401::AID-AJMG3>3.0.CO;2-C"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38141"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20143"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31873"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(78)81152-4"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19990611)84:5<396::AID-AJMG2>3.0.CO;2-L"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2004.11.035"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073807300292"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33188"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.37"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00247-013-2684-3"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2014.01.004"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/371252a0"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.11.1361"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90302-6"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320260426"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320370323"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/386288a0"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37231"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1086\/302275"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0395-321"},{"key":"e_1_2_6_25_1","unstructured":"American Journal of Medical Genetics Part A 173 4"},{"issue":"6","key":"e_1_2_6_26_1","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1111\/j.1471-4159.2006.04285.x","article-title":"Fibroblast growth factor receptor 3 kinase domain mutation increases cortical progenitor proliferation via mitogen\u2010activated protein kinase activation","volume":"100","author":"Thomson R. E.","year":"2006","journal-title":"Journal of Neurochemistry"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10062"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.96"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.29.11.831"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32085"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.38839","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.38839","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.38839","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.38839","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T09:10:35Z","timestamp":1720429835000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.38839"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7]]},"references-count":29,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2018,7]]}},"alternative-id":["10.1002\/ajmg.a.38839"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.38839","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"type":"print","value":"1552-4825"},{"type":"electronic","value":"1552-4833"}],"subject":[],"published":{"date-parts":[[2018,7]]},"assertion":[{"value":"2018-02-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}