Three novel PHEX gene mutations in four Chinese families with X-linked dominant hypophosphatemic rickets
Three novel PHEX gene mutations in four Chinese families with X-linked dominant hypophosphatemic rickets
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DOI：
10.1016/j.bbrc.2012.06.042
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发表时间：
2012-07-13
影响因子：
3.1
通讯作者：
Zhang, Zhen-lin
中科院分区：
文献类型：
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作者：
Kang, Qing-lin;Xu, Jia;Zhang, Zhen-lin
背景：X连锁低磷血症（XLH）是遗传性佝偻病最常见的形式，是一种显性疾病，其特征是肾磷酸盐消耗伴低磷血症、骨矿化异常、身材矮小和佝偻病表现。与XLH相关的失活突变基因已被鉴定为PHEX，它是一种磷酸盐调节基因，与X染色体上的内肽酶具有同源性。在这项研究中，在四个患有XLH的中国家庭中发现了多种PHEX突变。方法：我们通过使用PCR来分析突变并进行测序，调查了四个表现出XLH典型特征的无亲缘关系的中国家庭。实验室和放射学检查同时进行。结果：在这4个家系中发现了3个新突变：1个移码突变，第20号外显子出现c.2033dupT，导致p.T679H；外显子 11 中存在一个无义突变，c.1294A > T，导致 p.K432X；以及一个错义突变，即第 22 号外显子中的 c.2192T > C，导致 p.F731S。结论：我们发现 PHEX 基因突变是这些中国家族中 XLH 的原因。我们的研究结果有助于了解中国 XLH 患者的遗传基础。 (C) 2012 Elsevier Inc. 保留所有权利。
Background: X-linked hypophosphatemia (XLH), the most common form of inherited rickets, is a dominant disorder that is characterized by renal phosphate wasting with hypophosphatemia, abnormal bone mineralization, short stature, and rachitic manifestations. The related gene with inactivating mutations associated with XLH has been identified as PHEX, which is a phosphate-regulating gene with homologies to endopeptidases on the X chromosome. In this study, a variety of PHEX mutations were identified in four Chinese families with XLH.Methods: We investigated four unrelated Chinese families who exhibited typical features of XLH by using PCR to analyze mutations that were then sequenced. The laboratory and radiological investigations were conducted simultaneously.Results: Three novel mutations were found in these four families: one frameshift mutation, c.2033dupT in exon 20, resulting in p.T679H; one nonsense mutation, c.1294A > T in exon 11, resulting in p.K432X; and one missense mutation, c.2192T > C in exon 22, resulting in p.F731S.Conclusions: We found that the PHEX gene mutations were responsible for XLH in these Chinese families. Our findings are useful for understanding the genetic basis of Chinese patients with XLH. (C) 2012 Elsevier Inc. All rights reserved.