摘要目的 对3个疑诊为X-连锁低血磷抗维生素D佝偻病(X-linked hypophosphatemia,XLH)的家系进行PHEX基因的突变检测.方法 提取患者及其家系成员外周血的基因组DNA,用PCR扩增PHEX基因的全部外显子及其侧翼序列,用Sanger测序法检测潜在的突变,并在家系中进行基因型与表型的相关性分析,评价突变的致病性.结果 家系1检测出PHEX基因第8外显子c.871C＞T(p.R291X)致病突变;家系2检测出第15外显子c.1601C＞T(p.P534L)杂合致病突变;家系3检测出第11外显子c.1234delA(p.S412Vfs* 12)杂合突变,造成密码子阅读框发生移码,而使蛋白质翻译的提前终止,经查询HGMD数据库及国内外文献均未见报道.结论 检测出的3种PHEX基因突变可能是3个XLH家系的致病原因.新突变的发现扩展了PHEX基因的突变谱.

abstractsObjective To explore the molecular basis for three pedigrees affected with hypophosphatemia vitamin D resistant rickets (X-linked hypophosphatemia,XLH).Methods Peripheral blood samples from the three pedigrees were collected.Following DNA extraction,the 11 exons and flanking regions of the PHEX gene were subjected to PCR amplification and direct sequencing.Pathogenicity of identified mutations was evaluated through genotype-phenotype correlation.Results For pedigrees 1 and 2,pathogenic mutations were respectively identified in exon 8 (c.871C＞T,p.R291X) and exon 15 (c.1601C＞T,p.P534L) of the PHEX gene.For pedigree 3,a novel mutation (c.1234delA,p.S412Vfs * 12) was found in exon 11 of the PHEX gene,which caused shift the reading frame and premature termination of protein translation.Conclusion The three mutations probably account for the XLH in the affected pedigrees.The discovery of novel mutations has enriched the spectrum of PHEX gene mutations