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Identification of a Mutation in FGF23 Involved in Mandibular Prognathism

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-susce...

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Autores principales: Chen, Fengshan, Li, Qin, Gu, Mingliang, Li, Xin, Yu, Jun, Zhang, Yong-Biao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462018/
https://www.ncbi.nlm.nih.gov/pubmed/26059428
http://dx.doi.org/10.1038/srep11250
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author Chen, Fengshan
Li, Qin
Gu, Mingliang
Li, Xin
Yu, Jun
Zhang, Yong-Biao
author_facet Chen, Fengshan
Li, Qin
Gu, Mingliang
Li, Xin
Yu, Jun
Zhang, Yong-Biao
author_sort Chen, Fengshan
collection PubMed
description 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.
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spelling pubmed-44620182015-06-12 Identification of a Mutation in FGF23 Involved in Mandibular Prognathism Chen, Fengshan Li, Qin Gu, Mingliang Li, Xin Yu, Jun Zhang, Yong-Biao Sci Rep Article 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. Nature Publishing Group 2015-06-10 /pmc/articles/PMC4462018/ /pubmed/26059428 http://dx.doi.org/10.1038/srep11250 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Chen, Fengshan
Li, Qin
Gu, Mingliang
Li, Xin
Yu, Jun
Zhang, Yong-Biao
Identification of a Mutation in FGF23 Involved in Mandibular Prognathism
title Identification of a Mutation in FGF23 Involved in Mandibular Prognathism
title_full Identification of a Mutation in FGF23 Involved in Mandibular Prognathism
title_fullStr Identification of a Mutation in FGF23 Involved in Mandibular Prognathism
title_full_unstemmed Identification of a Mutation in FGF23 Involved in Mandibular Prognathism
title_short Identification of a Mutation in FGF23 Involved in Mandibular Prognathism
title_sort identification of a mutation in fgf23 involved in mandibular prognathism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462018/
https://www.ncbi.nlm.nih.gov/pubmed/26059428
http://dx.doi.org/10.1038/srep11250
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