Objective: To investigate PHEX gene mutations in 2 patients with X-linked hypophosphatemic rickets (XLH) and their families and to clarify the genetic etiology.
Methods: A retrospective analysis was performed for the clinical data of two patients with XLH. High-throughput sequencing was used to detect the PHEX gene, a pathogenic gene of XLH. PCR-Sanger sequencing was used to verify the distribution of mutations in families.
Results: Both patients had novel mutations in the PHEX gene; one patient had a frameshift mutation, c.931dupC, which caused early termination of translation and produced the truncated protein p.Gln311Profs*13; the other patient had a splice site mutation, IVS14+1G>A, which caused the skipping of exon 15 and produced an incomplete amino acid chain. Their parents had normal gene phenotypes.
Conclusions: c.931dupC and IVS14+1G>A are two novel mutations of the PHEX gene and might be the new pathogenic mutations of XLH.
目的: 研究2例X-连锁低血磷性佝偻病（XLH）患儿及家系磷酸盐调节基因（PHEX）的突变类型，以明确其遗传学病因。
方法: 回顾性分析2例XLH患者临床资料，应用高通量测序技术从基因组水平对先证者的XLH致病基因PHEX进行检测，并应用PCR-Sanger测序法对突变基因的家系分布进行验证。
结果: 2例患儿均检测到PHEX基因新发突变，1例为移码突变c.931dupC，导致翻译提前终止，产生截短蛋白p.Gln311Profs*13；另1例为剪接位点突变IVS14+1G > A，导致外显子15跳跃，产生不完整的氨基酸链。2例患儿父母的基因表型均正常。
结论: c.931dupC和IVS14+1G > A是PHEX基因的两个新突变，可能是XLH新的致病性突变。