title: A novel FGFR2 mutation in tyrosine kinase II domain, L617F, in Crouzon syndrome.
abstract: The purposes of this study were to find a novel mutation of FGFR2 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. FGFR2 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 Runx2 transcriptional activity, real-time PCR for the bone markers (osteocalcin and alkaline phosphatase), and Western blot for phosphorylated FGFR2 and ERK1/2-MAPK protein. Among 16 patients, 10 showed FGFR2 mutations that had already been reported elsewhere. A novel FGFR2 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. Runx2 transcriptional activity and expression of osteocalcin and alkaline phosphatase significantly increased in L617F-transfected cells compared to wild-type cells. FGFR2 autophosphorylation in L617F-transfected cells increased in 1% serum, but ERK1/2-MAPK protein was not activated. The FGFR2-L617F mutation associated with the TK domain is potentially related to premature suture closure in Crouzon syndrome patient.
authors.affiliation: Department of Orthodontics, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Republic of Korea.
authors.forename: Ye-Jin
authors.initials: YJ
authors.lastname: Suh
authors.forename: Han-Sol
authors.initials: HS
authors.lastname: Bae
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Choi
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Myung-Jin
authors.initials: MJ
authors.lastname: Kim
authors.forename: Sukwha
authors.initials: S
authors.lastname: Kim
authors.forename: Hyun-Mo
authors.initials: HM
authors.lastname: Ryoo
authors.forename: Seung-Hak
authors.initials: SH
authors.lastname: Baek
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D002675:Child, Preschool; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D003394:Craniofacial Dysostosis / Q000209:etiology / Q000235:genetics*; D005145:Face / Q000002:abnormalities; D005260:Female; D006801:Humans; D008297:Male; D008437:Maxilla / Q000002:abnormalities; D009154:Mutation; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D012150:Polymorphism, Restriction Fragment Length; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics* / Q000378:metabolism
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D015675:Osteocalcin; C496353:FGFR2 protein, human; D011505:Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D000469:Alkaline Phosphatase
keywords: CROUZON SYNDROME; L617F; NOVEL FGFR2 MUTATION; TYROSINE KINASE DOMAIN