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Whole exome sequencing demonstrated a novel, de novo 6 base pair tandem duplication in <jats:italic>FGFR3<\/jats:italic> that results in the insertion of Ser\u2010Phe after position Leu324. in vitro studies showed that this variant results in aberrant dimerization, excessive spontaneous phosphorylation of FGFR3 dimers and excessive, ligand\u2010independent tyrosine kinase activity. Together, these data suggest that this variant leads to constitutive disulfide bond\u2010mediated dimerization, and that this, surprisingly, occurs to an extent similar to the neonatal lethal thanatophoric dysplasia type I Ser249Cys variant.<\/jats:p>","DOI":"10.1002\/ajmg.a.62043","type":"journal-article","created":{"date-parts":[[2020,12,25]],"date-time":"2020-12-25T09:52:59Z","timestamp":1608889979000},"page":"798-805","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Typical achondroplasia secondary to a unique insertional variant of <scp><i>FGFR3<\/i><\/scp> with in vitro demonstration of its effect on <scp>FGFR3<\/scp> function"],"prefix":"10.1002","volume":"185","author":[{"given":"April N.","family":"Meyer","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry University of California San Diego  La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peggy","family":"Modaff","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Wisconsin  Madison Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clark G.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of California San Diego  La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Wohler","sequence":"additional","affiliation":[{"name":"McKusick\u2010Nathans Department of Genetic Medicine Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nara L.","family":"Sobreira","sequence":"additional","affiliation":[{"name":"McKusick\u2010Nathans Department of Genetic Medicine Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel J.","family":"Donoghue","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of California San Diego  La Jolla California USA"},{"name":"UCSD Moores Cancer Center  La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3471-5154","authenticated-orcid":false,"given":"Richard M.","family":"Pauli","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Wisconsin  Madison Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,12,24]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"169","article-title":"An uncommon G375C substitution in a newborn with achondroplasia","volume":"11","author":"Addor M. 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