Three novel mutations of the PHEX gene in three Chinese families with X-linked dominant hypophosphatemic rickets
Three novel mutations of the PHEX gene in three Chinese families with X-linked dominant hypophosphatemic rickets
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三个中国 X 连锁显性低磷血症性佝偻病家系 PHEX 基因的 3 个新突变
DOI：
10.1007/s00223-007-9067-4
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发表时间：
2007-12-01
影响因子：
4.2
通讯作者：
Zhou, Xueying
中科院分区：
文献类型：
--
作者：
Xia, Weibo;Meng, Xunwu;Zhou, Xueying
X连锁显性低磷血症（XLH，OMIM307800）是人类遗传性佝偻病中最常见的形式，是一种以生长迟缓、佝偻病和骨软化性骨病、低磷血症和肾性磷酸盐消耗为特征的磷酸盐稳态的显性障碍。负责XLH的基因通过定位克隆鉴定，并命名为PHEX（以前称为PEX），以描述与X染色体上的内肽酶同源的磷酸调节基因。最近，对PHEX基因的广泛突变分析揭示了XLH中多种基因缺陷。突变的种族分布非常广泛，但只有少数突变在中国已被报道。为分析3个无亲缘关系的XLH家系的分子基础，我们测定了患者PHEX基因和成纤维细胞生长因子23（FGF23）基因的核苷酸序列。同时测定这些XLH患者的血清FGF23浓度。在这3个家系中发现了3种不同的新突变：缺失突变c.264delG导致p.W88X，错义突变c.1673C > G导致p.P558A，无义突变c.1809G > A导致p.W603X。3个家系的XLH患者血清FGF23浓度均明显高于正常人。结果表明，PHEX基因突变是这些患者中XLH的原因，这些突变可能导致血清FGF23水平升高。
X-linked dominant hypophosphatemia (XLH, OMIM307800), the most prevalent form of inherited rickets in humans, is a dominant disorder of phosphate homeostasis characterized by growth retardation, rachitic and osteomalacic bone disease, hypophosphatemia, and renal phosphate wasting. The gene responsible for XLH was identified by positional cloning and designated PHEX (formerly PEX) to depict a phosphate-regulating gene homologous with endopeptidases on the X chromosome. Recently, extensive mutation analysis of the PHEX gene has revealed a wide variety of gene defects in XLH. The ethnic distribution of the mutations is very widespread but only a few mutations in Chinese have been reported. To analyze the molecular basis in three unrelated Chinese families with XLH, we determined the nucleotide sequence of the PHEX gene and fibroblast growth factor 23 (FGF23) gene of affected members. The serum FGF23 concentrations of these patients with XLH were also measured. Three different novel mutations were observed in these three families: one deletion mutation c.264delG causing p.W88 X; one missense mutation c.1673C > G causing p.P558A; one nonsense mutation c.1809G > A causing p.W603 X. Serum concentration of FGF23 in XLH patients of these three families was significantly higher than normal. The results suggest that PHEX gene mutations were responsible for XLH in these patients and these mutations may contribute to a higher serum FGF23 level.