中国南方汉族人3个家族性激素耐药型肾病综合征家系CD2AP和NPHS1基因突变分析  

Mutational Analysis of CD2AP and NPHS1 Gene in 3 Families from Southern Chinese Han Ethnic Group with Steroid-Resistant Nephrotic Syndrome

作　　者：孟大川[1,2] 王道静[1,2] 余自华[1,2] 付荣[2] 王晶晶[2] 陈新民[2] 叶礼燕[2] 

机构地区：[1]福建医科大学福州总医院临床医学院儿科,福州350025 [2]南京军区福州总医院儿科,福州350025

出　　处：《实用儿科临床杂志》2011年第5期329-332,344,共5页Journal of Applied Clinical Pediatrics

基　　金：福建省自然科学基金(2006J0119);南京军区医学科学技术研究"十一.五"计划课题(06MA148;06MA151);南京军区医学科技创新课题(08MA102)

摘　　要：目的分析中国南方汉族人家族性激素耐药型肾病综合征(SRNS)家系CD2AP和NPHS1基因突变及其特点。方法研究对象为A、B、C 3个南方汉族SRNS家系先证者及其父母,A、B 2个家系先证者的姐姐和50例尿检正常的南方汉族成年人。取所有研究对象外周静脉血,提取基因组DNA,PCR方法扩增CD2AP基因全部18个外显子和NPHS1基因全部29个外显子及其周围的部分内含子,对PCR产物直接进行DNA序列测定。结果在3个SRNS家系先证者未检测出CD2AP基因致病突变。在B家系的先证者检测出NPHS1基因2398C>T(R800C)杂合突变,先证者父亲亦携带此杂合突变,但先证者母亲及姐姐未发现该突变。在50例对照人群中未发现2398C>T突变。此外,在3个先证者及50例对照人群还检测出9种已报道的CD2AP基因多态性——IVS4-25G>A、IVS8-95G>A、IVS10+36C>A、IVS10-153A>T、IVS10-110A>G、IVS11+82T>C、1204C>T、IVS16+24G>A、IVS17-66T>C和4种已报道的NPHS1基因多态性——349G>A、IVS24+36C>T、3315G>A和IVS27+45C>T。结论在1个中国南方汉族SRNS家系先证者检测出NPHS1基因突变——2398C>T,证实中国南方汉族人家族性SRNS儿童存在NPHS1基因突变,提示对其需进行NPHS1基因突变分析。Objective To analyze the mutations and their feature of the CD2AP and NPHS1 gene in children with familial steroid-resistant nephrotic syndrome（SRNS） in Southern Chinese Han ethnic group. Methods Peripheral blood samples were collected for genetic analysis from probands of 3 Chinese families and their parents,and 2 probands′ siblings,and a normal control group of 50 healthy volunteers.Genomic DNA was isolated from peripheral blood leucocytes.Eighteen exons and exon-intron boundaries of CD2AP and 29 exons and exon-intron boundaries of NPHS1 were amplified by polymerase chain reaction.Mutational analysis was performed by DNA sequencing directly. Results No mutation in CD2AP was identified in 3 probands.A heterozygous missense mutation of 2398CT in exon 18 of NPHS1,which produced a hydrophilic arginine to cysteine change,was detected in the proband of the Chinese family B,whereas it was not found in the 50 controls.The heterozygous mutation of 2398CT was also identified in the proband′s father,whereas it was not detected in her mother and sister.Moreover,9 already reported variants of CD2AP,IVS4-25GA,IVS8-95GA,IVS10＋36CA,IVS10-153AT,IVS10-110AG,IVS11＋82TC,1204CT,IVS16＋24GA and IVS17-66TC,and 4 already reported variants of NPHS1,349GA,IVS24＋36CT,3315GA and IVS27＋45CT,were found in 3 probands and some controls,indicating that all these varia-nts were gene polymorphisms. Conclusions A heterozygous mutation of 2398CT in NPHS1 was identified in one of the 3 probands with familial SRNS in Southern Chinese Han ethnic group,which indicates that NPHS1 mutaiton existed in children with familial SRNS in Southern Chinese Han ethnic group.The investigation suggests the necessary of performing the mutational analysis of NPHS1 in children with familial SRNS in Southern Chinese Han ethnic group.

关 键 词：激素耐药型肾病综合征 CD2AP基因 NPHS1基因 突变 汉族人 

分 类 号：R692.3[医药卫生—泌尿科学]