@article{4fcbaf9aecb94f6ca6ae98bf30d2a244,
title = "Typical achondroplasia secondary to a unique insertional variant of FGFR3 with in vitro demonstration of its effect on FGFR3 function",
abstract = "We describe an individual in whom clinical and radiographic features are typical for achondroplasia, but in whom the common variants of FGFR3 that result in achondroplasia are absent. Whole exome sequencing demonstrated a novel, de novo 6 base pair tandem duplication in FGFR3 that results in the insertion of Ser-Phe after position Leu324. in vitro studies showed that this variant results in aberrant dimerization, excessive spontaneous phosphorylation of FGFR3 dimers and excessive, ligand-independent tyrosine kinase activity. Together, these data suggest that this variant leads to constitutive disulfide bond-mediated dimerization, and that this, surprisingly, occurs to an extent similar to the neonatal lethal thanatophoric dysplasia type I Ser249Cys variant.",
keywords = "achondroplasia, fibroblast growth factor receptor 3, in vitro functional studies",
author = "Meyer, {April N.} and Peggy Modaff and Wang, {Clark G.} and Elizabeth Wohler and Sobreira, {Nara L.} and Donoghue, {Daniel J.} and Pauli, {Richard M.}",
note = "Funding Information: Whole exome sequence studies were completed with support of the Baylor‐Hopkins Center for Mendelian Genomics (NHGRI UM1 HG006542). This work was also supported by generous support from the UC San Diego Foundation. We thank Marvin Miller, M.D., Dennis Weiner M.D. Michael Bober M.D., Ph.D. and Elaine Spector, Ph.D. for their contributions. None of the authors declare a conflict of interest. The data upon which this article is based are not publicly available due to privacy restrictions. Funding Information: Whole exome sequence studies were completed with support of the Baylor-Hopkins Center for Mendelian Genomics (NHGRI UM1 HG006542). This work was also supported by generous support from the UC San Diego Foundation. We thank Marvin Miller, M.D., Dennis Weiner M.D. Michael Bober M.D., Ph.D. and Elaine Spector, Ph.D. for their contributions. None of the authors declare a conflict of interest. The data upon which this article is based are not publicly available due to privacy restrictions. Publisher Copyright: {\textcopyright} 2020 Wiley Periodicals LLC",
year = "2021",
month = mar,
doi = "10.1002/ajmg.a.62043",
language = "English (US)",
volume = "185",
pages = "798--805",
journal = "American Journal of Medical Genetics, Part A",
issn = "1552-4825",
publisher = "Wiley-Liss Inc.",
number = "3",
}