中文摘要：

目的研究低血磷抗维生素D佝偻病即X连锁低磷酸盐血症（XLH）患者发病的分子遗传学机制,揭示其基因型与表现型的相互关系,为实施有效的对症治疗和今后的孕早期产前基因诊断创造必要的前提条件。方法在临床初诊的基础上,采用PCR及扩增产物直接测序法对先证者的PHEX基因进行全面的突变检测;在检出PHEX基因c.2197-2198insAACT新突变后,采用PCR-DHPLC筛检法对随机采集的108例正常对照的相应外显子进行快速的突变筛查,以排除多态性变异的可能性,同时采用生物信息学方法对突变部位氨基酸的保守性和突变蛋白的二、三级结构进行预测分析,从而对其致病性进行鉴定。结果 （1）先证者PHEX基因第22外显子区域内存在一个新的杂合插入突变即c.2197-2198insAACT。（2）108例正常对照的DHPLC筛检和序列分析中,均未检测到c.2197-2198insAACT突变。（3）蛋白质二级、三级结构预测结果显示：c.2197-2198insAACT新突变引起密码子发生移位,导致肽链提前在第733位遇上终止密码TAA,致使肽链从正常的749个氨基酸缩短至732个,导致蛋白质二、三级结构发生明显改变,而正常对照无此变化。结论 PHEX基因c.2197-2198insAACT插入突变不是一般的多态性变异,而可能是一种新的致病性突变,它极可能是引起先证者发病的根本内因。

英文摘要：

Objective To study the molecular genetic mechanism of hypophosphatemic vitamin D resistant rickets（X-linked hypophosphatemia,XLH）,and reveal the relationship between the genotype and phenotype,and provide a basis for effective symptomatic treatment and prenatal gene diagnosis in the future.Methods Mutation detection was performed on the proband with PCR and direct sequencing of PCR products.After the novel mutation of c.2197-2198insAACT in PHEX gene was detected,PCR-DHPLC was used to analysis 108 randomly selected healthy controls in exon22 of the PHEX gene,in order to rule out the possibility of polymorphism,at the same time,bioinformatic approaches for protein secondary,tertiary structure prediction were applied to identify the novel pathologic mutation.Results（1）One novel heterozygous insertion mutation（c.2197-2198insAACT）in exon22 of PHEX gene was found in patient.（2）No＇c.2197-2198insAACT＇mutation was found among 108 cases of unaffected controls.（3）The results of protein secondary and tertiary structure prediction showed that the novel mutation（c.2197-2198insAACT）led to premature translational termination at amino acid position 733（p.C733X）,thus the peptide chain was shortened from 749 to 732 amino acids,and secondary and tertiary protein structure change,which were not found in all the controls.Conclusions The novel insertion mutation（c.2197-2198insAACT）in PHEX gene probably is a novel pathologic mutation but not a polymorphism,which may be responsible for the patient with XLH.