A dominant negative FGFR1 mutation identified in a Kallmann syndrome patient
A dominant negative FGFR1 mutation identified in a Kallmann syndrome patient
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在卡尔曼综合征患者中发现显性阴性 FGFR1 突变
DOI：
10.1016/j.gene.2017.04.017
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发表时间：
2017-07-20
期刊：
影响因子：
3.5
通讯作者：
Li, Jia-Da
中科院分区：
文献类型：
--
作者：
Luo, Hunjin;Zheng, Ruizhi;Li, Jia-Da
卡尔曼综合征（Kallmann syndrome， KS）以孤立性促性腺功能减退（IHH）伴嗅觉缺失为特征。成纤维细胞生长因子受体1 （FGFR1）是ks相关基因之一，约占总患者的10%。FGFR1突变也在更严重的颅缝闭塞综合征中被发现，颅缝闭塞综合征相关的FGFR1突变子集显示出显性的负面影响。在这项研究中，我们在一名KS患者中发现了一种新的FGFR1突变（c.867G > a; p.W289X）。p.W289X突变导致过早终止，产生没有跨膜和细胞内结构域的截短的FGFR1。确实，W289X FGFR1被分泌到培养基中。此外，W289X FGFR1干扰野生型受体的功能，诱导ERK1/2磷酸化。因此，我们在KS患者中发现了显性阴性FGFR1突变，该突变FGFR1可能用于破译FGFR1的生理功能。
Kallmann syndrome (KS) is characterized by isolated hypogonadotropic hypogonadism (IHH) with anosmia. Fibroblast growth factor receptor 1 (FGFR1) is one of KS-associated genes, accounts for approximately 10% of total patients. FGFR1 mutations have also been identified in more severe craniosynostosis syndromes, and a subset of craniosynostosis syndromes-associated FGFR1 mutations show dominant negative effect. In this study, we identified a novel FGFR1 mutation (c.867G > A; p.W289X) in a KS patient. The p.W289X mutation leads premature termination, producing a truncated FGFR1 without the transmembrane and intracellular domains. Indeed, the W289X FGFR1 was secreted into culture medium. Further, W289X FGFR1 interfered with the function of wild type receptor to induce ERK1/2 phosphorylation. We therefore identified a dominant negative FGFR1 mutation in the KS patient, and this mutant FGFR1 may be used to decipher the physiological function of FGFR1.