Novel de novo nonsense mutation of the PHEX gene (p.Lys50Ter) in a Chinese patient with hypophosphatemic rickets
Novel de novo nonsense mutation of the PHEX gene (p.Lys50Ter) in a Chinese patient with hypophosphatemic rickets
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DOI：
10.1016/j.gene.2015.03.066
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发表时间：
2015-07-01
期刊：
影响因子：
3.5
通讯作者：
Wu, Lingqian
中科院分区：
文献类型：
--
作者：
Huang, Yanru;Mei, Libin;Wu, Lingqian
X连锁低磷血症性佝偻病（XLHR）是遗传性佝偻病中最常见的一种，是一种以低磷血症、骨矿化异常和身材矮小为特征的显性疾病。PHEX基因突变是XLHR的主要原因。在此，我们的临床特点是四个不相关的家庭与低磷酸盐血症，骨异常，身材矮小，牙本质畸形。使用桑格测序对PHEX基因进行突变分析，发现三个复发突变（c.2197 T>C、c.1646 G>C和c.2198 G>A）和一个从头无义突变（c.148 A>T）。在任何未受影响的家族成员或100名健康对照中均未发现新突变，并预测会产生截短蛋白（p.K50X），这是XLHR个体中经常检测到的由无义突变引起的PHEX蛋白截短形式。因此，我们的工作表明，c.148A>T（p.K50X）突变可能是第2个家系中III-2个体的致病突变，PHEX基因突变可能是导致这些中国家系XLHR的原因。这些发现扩大了PHEX的突变谱，并可能有助于我们了解XLHR的分子基础，以促进遗传咨询。(C)2015 Elsevier B. V.版权所有。
X-linked hypophosphatemic rickets (XLHR), the most common form of inherited rickets, is a dominant disorder characterized by hypophosphatemia, abnormal bone mineralization, and short stature. Mutations in the PHEX gene are major causes of XLHR. Herein, we clinically characterized four unrelated families with hypophosphatemia, bone abnormalities, short stature, and dentin malformation. Mutational analysis of the PHEX gene using Sanger sequencing revealed three recurrent mutations (c.2197 T>C, c.1646G>C, and c.2198G>A) and a de novo nonsense mutation (c.148A>T). The novel mutation was not found in any of the unaffected family members or in the 100 healthy controls and was predicted to produce a truncated protein (p.K50X), a truncated form of the PHEX protein caused by nonsense mutations has been frequently detected in XLHR individuals. Thus, our work indicated that the c.148A>T (p.K50X) mutation was the likely pathogenic mutation in individual III-2 in family 2, and that PHEX gene mutations were responsible for XLHR in these Chinese families. These findings expand the mutation spectrum of PHEX and may help us to understand the molecular basis of XLHR in order to facilitate genetic counseling. (C) 2015 Elsevier B.V. All rights reserved.