3例低血磷性抗维生素D佝偻病的基因诊断及文献复习

对3例临床疑似X连锁低血磷抗维生素D佝偻病（XLH）患儿进行磷酸盐调节基因（PHEX）分析并确诊的临床资料进行回顾性分析及相关文献复习，探讨中国人存在的突变热点和突变类型。3例患儿均检测到PHEX基因突变，1例为无义突变（c.58C>T），2例为剪接突变（c.1645+1G>A，c.436+1G>A），其中c.436+1G>A为新突变。至2014年1月，世界上已报道的PHEX基因突变共有329个，错义突变占数量最多（24%），突变热点区域有3个。不同地区的病例总数和突变类型存在差异。中国人群中，89例XLH病人进行了PHEX基因检测，发现28种突变，其中在22外显子上发现的突变数量最多（18%），突变类型最多的为错义突变（61%）。总之，在中国人群中，XLH病人PHEX基因最常见的突变位置为第22外显子，最常见的突变类型为错义突变；c.436+1G>A 为PHEX基因的新突变。

Three PHEX gene mutations in Chinese subjects with hypophosphatemic rickets and literature review

The clinical data of three Chinese children who had been definitely diagnosed with X-link dominate hypophosphatemic rickets (XLH) by gene mutation analysis of phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) were retrospectively studied and the relevant literature was reviewed. PHEX gene mutations were detected in all 3 XLH children; a nonsense mutation (c.58C>T) in one case and splicing mutations (c.1645+1G>A, c.436+1G>A) in the other two cases. Among these mutations, c.436+1G>A was novel. As of January 2014, a total of 329 PHEX gene mutations were reported, primarily within three mutation hot spots, throughout the world. Missense mutations accounted for the highest proportion (24%) among all mutations. There is literature showing geographic differences in the total number of XLH subjects and PHEX mutation types across the world. In the current literature, 89 cases of XLH with 28 types of PHEX mutations have been reported in the population of mainland China. Exon 22 is the most frequent mutation site (18%) and missense mutations are the most common type of mutations (61%). It is concluded that exon 22 is the mutation hot spot and missense mutation is the most common type of mutation in the PHEX gene in Chinese XLH patients and that c.436+1G>A detected in this study is a novel PHEX gene mutation in Chinese with XLH.