A Novel FGFR2 Mutation in Tyrosine Kinase II Domain, L617F, in Crouzon Syndrome. Issue 1 (January 2014)

• Record Type: Journal Article
• Authors: Suh, Ye‐Jin; Bae, Han‐Sol; Choi, Jin‐Young; Lee, Jong‐Ho; Kim, Myung‐Jin; Kim, Sukwha; Ryoo, Hyun‐Mo; Baek, Seung‐Hak
• Is Part Of: Journal of cellular biochemistry. Volume 115:Issue 1(2014:Jan.)
• Page Start: 102
• Page End: 110
• Publication Date: 2014-01
• Subjects: Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.24637
• Languages: English
• ISSNs: 0730-2312

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>ABSTRACT</title> <sec id="jcb24637-sec-0001" sec-type="section"> <p>The purposes of this study were to find a novel mutation of <italic>FGFR2</italic> in Korean Crouzon syndrome patients and to identify the functional consequences of this mutation. The samples consisted of 16 Crouzon patients. Peripheral venous blood was collected from the patients. <italic>FGFR2</italic> mutation screening was performed by direct PCR sequencing of all exons and part of the introns. Restriction fragment length polymorphism (RFLP) analysis was performed to confirm the novel mutation. For functional studies, we performed luciferase assay for <italic>Runx2</italic> transcriptional activity, real‐time PCR for the bone markers (osteocalcin and alkaline phosphatase), and Western blot for phosphorylated <italic>FGFR2</italic> and <italic>ERK1/2‐MAPK</italic> protein. Among 16 patients, 10 showed <italic>FGFR2</italic> mutations that had already been reported elsewhere. A novel <italic>FGFR2</italic> mutation associated with tyrosine kinase II (TK‐II) domain, L617F, was found in one Crouzon syndrome patient by direct PCR sequencing. Presence of this mutation was confirmed using RFLP analysis. <italic>Runx2</italic> transcriptional activity and expression of osteocalcin and alkaline phosphatase significantly increased in L617F‐transfected cells compared to wild‐type cells. <italic>FGFR2</italic> autophosphorylation in L617F‐transfected cells increased in 1% serum, but <italic>ERK1/2‐MAPK</italic> protein was not activated. The <italic>FGFR2</italic>‐L617F mutation associated with the TK domain is potentially related to premature suture closure in Crouzon syndrome patient. J. Cell. Biochem. 115: 102–110, 2014. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>