title: Contribution of FGFR1 Variants to Craniofacial Variations in East Asians.
abstract: FGFR1 plays an important role in the development of the nervous system as well as the regulation of the skeletal development and bone homeostasis. Mutations in FGFR1 genes affect skull development, specifically suture and synchondrosis, resulting in craniosynostosis and facial abnormalities. We examined subjects with normal skull morphology for genetic polymorphisms that might be associated with normal craniofacial variations. Genomic DNA was obtained from 216 Japanese and 227 Korean subjects. Four FGFR1 SNPs, namely, rs881301, rs6996321, rs4647905, and rs13317, were genotyped. These SNPs were tested for association with craniofacial measurements obtained from lateral and posteroanterior cephalometries, in which principle component analysis was performed to compress the data of the craniofacial measurements. We observed that SNPs rs13317 and rs6996321 were correlated with the overall head size and midfacial development, indicating that FGFR1 SNPs played crucial roles in the normal variation of human craniofacial morphology. Subjects with the derived alleles of SNPs rs13317 and rs6996321 had a small face and a facial pattern associated with a retruded midface and relatively wide-set eyes. These facial features were similar to but were milder than those of individuals with Pfeiffer syndrome, which is caused by a dysfunctional mutation in FGFR1.
authors.affiliation: Department of Orthodontics, Showa University, Tokyo, Japan.|Department of Orthodontics, Suez Canal University, Ismailia, Egypt.
authors.forename: Mohamed
authors.identifier: http://orcid.org/0000-0002-9302-0443
authors.initials: M
authors.lastname: Adel
authors.affiliation: Department of Orthodontics, Showa University, Tokyo, Japan.
authors.forename: Tetsutaro
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Department of Orthodontics, Showa University, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tomita
authors.affiliation: Department of Orthodontics, Showa University, Tokyo, Japan.
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Nakawaki
authors.affiliation: Department of Orthodontics, Dental Research Institute, Pusan National University Dental Hospital, Yangsan, South Korea.
authors.forename: Yong-Il
authors.initials: YI
authors.lastname: Kim
authors.affiliation: Department of Orthodontics, Showa University, Tokyo, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hikita
authors.affiliation: Department of Orthodontics, Showa University, Tokyo, Japan.
authors.forename: Shugo
authors.initials: S
authors.lastname: Haga
authors.affiliation: Department of Orthodontics, Showa University, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Department of Orthodontics, Suez Canal University, Ismailia, Egypt.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Nadim
authors.affiliation: Department of Human Biology and Anatomy, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kawaguchi
authors.affiliation: Department of Human Biology and Anatomy, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Isa
authors.affiliation: Department of Orthodontics, Alexandria University, Alexandria, Egypt.
authors.forename: Walid H
authors.initials: WH
authors.lastname: El-Kenany
authors.affiliation: Department of Orthodontics, Suez Canal University, Ismailia, Egypt.
authors.forename: Abbadi A
authors.initials: AA
authors.lastname: El-Kadi
authors.affiliation: Department of Orthodontics, Dental Research Institute, Pusan National University Dental Hospital, Yangsan, South Korea.
authors.forename: Soo-Byung
authors.initials: SB
authors.lastname: Park
authors.affiliation: Department of Human Biology and Anatomy, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Ishida
authors.affiliation: Department of Orthodontics, Showa University, Tokyo, Japan.
authors.forename: Koutaro
authors.initials: K
authors.lastname: Maki
authors.affiliation: Department of Human Biology and Anatomy, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kimura
mesh_terms: D000168:Acrocephalosyndactylia / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D002508:Cephalometry; D019465:Craniofacial Abnormalities / Q000235:genetics* / Q000473:pathology; D003398:Craniosynostoses / Q000235:genetics* / Q000473:pathology; D005145:Face / Q000033:anatomy & histology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics*; D012886:Skull / Q000033:anatomy & histology
chemical_list: C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1