中国南方汉族散发性先天性肾病综合征NPHS1基因突变1例

Mutation of NPHS1 Gene in A Child with Congenital Nephrotic Syndrome in Southern Chinese Han Ethnic Group

目的分析中国南方汉族1例散发性先天性肾病综合征(CNS)患儿NPHS1基因突变及其特点。方法研究对象为1例中国南方汉族CNS患儿及其父母,对照人群为50例尿液检查正常的南方汉族成年人。取所有研究对象外周静脉血3 mL,提取基因组DNA,PCR扩增NPHS1全部29个外显子及其周围的部分内含子和启动子全长序列,对PCR产物直接进行DNA序列测定。结果在CNS患儿检测出NPHS1基因3250insG(V1084fsX1095)纯合突变,其父母分别携带3250insG杂合突变。在CNS患儿及其父母还检测出3种已报道的NPHS1基因多态性——349G>A、3315G>A和IVS27+45C>T。在50例对照人群中未发现NPHS1基因3250insG变异;但检测出349G>A、3315G>A和IVS27+45C>T基因多态性。结论首次在1例中国南方汉族CNS患儿发现了NPHS1基因纯合突变——3250insG(V1084fsX1095),表明中国南方汉族散发性CNS患儿存在NPHS1基因突变,提示对中国南方汉族散发性CNS患儿需进行NPHS1基因突变分析。

Objective To analyze the mutations and characteristics of NPHS1 gene in a child with congenital nephrotic syndrome（CNS） in Southern Chinese Han ethnic group. Methods Peripheral blood samples were collected for genetic analysis from the child with CNS and his parents with normal urinalysis,and 50 unrelated adult volunteers whose urinalysis were normal in Southern Chinese Han ethnic group stu-dies as the controls.Genomic DNA was isolated from peripheral blood leucocytes.Twenty-nine exons and exon-intron boundaries of the NPHS1 gene were amplified by polymerase chain reaction（PCR）.Mutational analysis was performed by DNA sequencing directly. Results A homozygous mutation 3250insG,which caused a frame shift and a 1095-residue trucated protein,in exon 24 of the NPHS1 gene was identified in the child with CNS,whereas it was not found in the 50 controls.A heterozygous mutation of 3250insG was also detected in the child′s parents,respectively.Moreover,3 already published NPHS1 polymorphisms,349GA,3315GA and IVS27＋45CT,were detected in the child and his parents,whereas it was also found in 50 controls. Conclusions A homozygous mutation in the NPHS1 gene was identified in the child with CNS in Southern Chinese Han ethnic group for the first time.The results demonstrate that NPHS1 gene mutations are also presented in children with sporadic CNS in Southern Chinese Han ethnic group.It suggests that there is the necessity of searching for mutations in NPHS1 gene in the children with sporadic CNS in Southern Chinese Han ethnic group.