title: Identification of a Mutation in FGF23 Involved in Mandibular Prognathism.
abstract: Mandibular prognathism (MP) is a severe maxillofacial disorder with undetermined genetic background. We collected a Chinese pedigree with MP which involved in 23 living members of 4 generations. Genome-wide linkage analysis were carried out to obtain the information in this family and a new MP-susceptibility locus, 12pter-p12.3 was identified. Whole-exome sequencing identified a novel heterozygous mutation in fibroblast growth factor (FGF) 23 (; p.A12D) which well segregated with MP in this pedigree within the locus. The mutation was also detected in 3 cases out of 65 sporadic MP patients, but not in any of the 342 control subjects. The p.A12D mutation may disrupt signal peptide function and inhibit secretory in FGF23. Furthermore, mutant FGF23 was overexpressed in 293T cells, increased cytoplasmic accumulation was observed compared with the wild type. We have discovered that c.35C>A mutation in FGF23 strongly associated with MP, which expand our understanding of the genetic contribution to MP pathogenesis.
authors.affiliation: Laboratory of Oral Biomedical Science and Translational Medicine, School and Hospital of Stomatology, Tongji University, Shanghai, P. R. China.
authors.forename: Fengshan
authors.initials: F
authors.lastname: Chen
authors.affiliation: Laboratory of Oral Biomedical Science and Translational Medicine, School and Hospital of Stomatology, Tongji University, Shanghai, P. R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Beijing Institute of Genomics, Chinese Academy of Sciences and Key Laboratory of GenomeScience and Information, Chinese Academy of Sciences, Beijing, P. R. China.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Gu
authors.affiliation: Department of Cardiology, Beijing Anzhen Hospital of the Capital University of Medical Sciences, Beijing, P. R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Beijing Institute of Genomics, Chinese Academy of Sciences and Key Laboratory of GenomeScience and Information, Chinese Academy of Sciences, Beijing, P. R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.affiliation: Beijing Institute of Genomics, Chinese Academy of Sciences and Key Laboratory of GenomeScience and Information, Chinese Academy of Sciences, Beijing, P. R. China.
authors.forename: Yong-Biao
authors.initials: YB
authors.lastname: Zhang
mesh_terms: D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics*; D006801:Humans; D008297:Male; D008334:Mandible / Q000002:abnormalities*; D009154:Mutation; D010375:Pedigree; D011378:Prognathism / Q000235:genetics*
chemical_list: C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23