摘要目的：分析来源于中国的4个家系6例家族性低磷性抗维生素 D 佝偻病（FHVDRR）患者的PHEX、FGF-23和 DMP-I 基因突变情况。方法采集4个 FHVDRR 家系成员及10例健康对照者的外周血血样，提取基因组 DNA，聚合酶链反应（PCR）扩增，采用 DNA 直接测序法及 TA 克隆进行 PHEX、FGF-23、DMP-I基因的外显子及侧翼序列测序，分析其基本突变。结果家系1中先证者及先证者姐姐在 DMP-I 基因第6外显子处发现 DMP-I 基因纯合同义突变（c1218 C ﹥ T，c1230 G ﹥ A），先证者母亲发现 DMP-I 基因杂合同义突变（c1218 C ﹥ T，c1230 G ﹥ A）。家系2中先证者在 PHEX 基因第12外显子处发现 PHEX 基因突变（c1333-1334 GC ﹥ TT，p. A445F），TA 克隆确认其为杂合突变，其父母及健康对照未发现相同突变；先证者及其母亲在FGF-23基因第3外显子处发现杂合突变（c716 C ﹥ T，p. T239M）。家系3中先证者在 DMP-I 基因第6外显子处发现 DMP-I 基因纯合突变（c205 A ﹥ T，p. S69C）；同时发现在先证者和其父的 FGF-23基因第3外显子处 c716 C ﹥ T，p. T239M 突变。家系1、3、4中先证者及其他受累者未发现 PHEX、FGF-23、DMP-I 基因致病突变。结论PHEX 基因 c1333-1334 GC ﹥ TT，p. A445F 突变可能是家系2中先证者患病病因，需进一步实验验证。家系2和家系3中发现的 FGF-23基因 c716 C ﹥ T，p. T239M 突变，尚不确定其为发病原因，认为其不引起表型异常。

abstractsObjective To evaluate the frequency of mutations that occur in PHEX,FGF - 23 and DMP - I genes associated with familial hypophosphatemic vitamin D resistant rickets among 6 patients from 4 families in China. Methods The peripheral blood samples from 4 families were collected and other 10 persons from different families were selected as normal controls,and then the total gene DNA was extracted from the whole blood. Using polymerase chain reaction(PCR)amplication,sequences of the exons and flanking zones in PHEX,FGF - 23 and DMP - I genes were sequenced by direct DNA sequencing and TA cloning,and then the mutations found were analyzed. Results In exon 6 of DMP - I gene,c1218 C ﹥ T and c1230 G ﹥ A mutations were detected in lineage 1,as same sense mutation (propositus and its sister:homozygous mutation;mother:heterozygous mutation);c1333 - 1334 GC ﹥ TT mutation,as missense mutation,was found in exon 12 of PHEX gene on the propositus of lineage 2,determined as heterozygous muta-tion,but the same mutation was not found from their parents. In exon 3 of FGF - 23 gene,c716 C ﹥ T,p. T239M hetero-zygous mutation was found on the propositus and its mother. In exon 6 of the DMP - I gene,c205 A ﹥ T homozygous mutation was detected in lineage 3. In lineage 3,c716 C ﹥ T mutation of the FGF - 23 gene was detected,and the pro-positus and their father had the same mutation. No disease causing mutations of the PHEX,FGF - 23 and DMP - I genes were detected in the family members of lineage 1,3 and 4. Conclusions The mutation c1333 - 1334 GC ﹥ TT detected in exon 12 of PHEX gene might be the cause of disease for the propositus of lineage 2,as missense mutation, which needs further verification;c716 C ﹥ T,p. T239M mutation of the FGF - 23 gene detected in lineage 2 and 3 might not be the causes of the hypophosphatemic rickets and abnormal phenotype.