Identification of a Mutation in FGF23 Involved in Mandibular Prognathism
Identification of a Mutation in FGF23 Involved in Mandibular Prognathism
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鉴定与下颌前突相关的 FGF23 突变
DOI：
10.1038/srep11250
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发表时间：
2015-06-10
影响因子：
4.6
通讯作者：
Zhang, Yong-Biao
中科院分区：
文献类型：
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作者：
Chen, Fengshan;Li, Qin;Zhang, Yong-Biao
下颌无颌症是一种严重的颌面部疾病，其遗传背景尚不清楚。我们收集了一个中国人MP家系，共涉及四代23名成员。对该家系进行全基因组连锁分析，发现了一个新的MP易感基因位点12 pter-p12.3。全外显子组测序鉴定了成纤维细胞生长因子（FGF）23（; p.A12D）中的一种新型杂合突变，该突变在该家系中与MP在该基因座内分离良好。65例散发性MP患者中也有3例检测到该突变，但342例对照受试者中均未检测到该突变。P.A12D突变可能破坏信号肽功能并抑制FGF 23的分泌。此外，突变型FGF 23在293 T细胞中过表达，与野生型相比观察到细胞质积累增加。我们已经发现FGF 23中的c.35C>A突变与MP强烈相关，这扩展了我们对MP发病机制的遗传贡献的理解。
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.