中国南方汉族激素耐药型肾病综合征儿童NPHS2基因突变分析

发布时间：2018-09-09 16:04

【摘要】：第一部分中国南方汉族散发性激素耐药型肾病综合征儿童NPHS2基因突变分析目的分析中国南方汉族散发性激素耐药型肾病综合征（steroid-resistantnephrotic syndrome，SRNS）儿童NPHS2基因突变及其特点。方法研究对象为52例中国南方汉族散发性SRNS患儿，对照人群为50例尿检正常的健康志愿者。取所有研究对象外周静脉血3ml，提取基因组DNA；PCR扩增NPHS2基因全部外显子及其周围的部分内含子；应用DNA序列直接测定法对PCR产物进行测序。结果在1例南方汉族散发性SRNS患儿中检出NPHS2基因杂合突变—148CT（R50W），突变检出率为1.9%。此外，还检出4个已报道的NPHS2基因多态性—102AG、288CT、954CT和1038AG；它们在52例SRNS患儿中的基因型和等位基因频率与其在50例正常对照人群中的基因型和等位基因频率分别比较，P值均＞0.05。结论中国南方汉族散发性SRNS患儿存在NPHS2基因突变，提示对中国南方汉族散发性SRNS患儿需进行NPHS2基因突变分析。第二部分中国南方汉族家族性激素耐药型肾病综合征家系NPHS2基因突变分析目的分析中国南方汉族家族性激素耐药型肾病综合征（steroid-resistantnephrotic syndrome，SRNS）家系NPHS2基因突变及其特点。方法研究对象为一个中国南方汉族家族性SRNS家系中的先证者及其姐和父母，对照人群为50例尿检正常的健康志愿者。取所有研究对象外周静脉血3ml，提取基因组DNA；PCR扩增NPHS2基因全部外显子及其周围的部分内含子和启动子区全长序列；应用DNA序列直接测定法对PCR产物进行测序。结果本研究在一个中国南方汉族家族性SRNS家系中先证者的NPHS2基因8个外显子和周围部分内含子及启动子区全长未检出致病突变。在先证者及其姐和父母的NPHS2基因外显子1检出1个变异—102AG（G34G），，在NPHS2基因启动子区检出3个变异—-1000AT、-670CT和-537_-531delCTTTTTT。这4个NPHS2基因变异在50例正常对照人群中均有检出，为已知的NPHS2基因多态性。结论NPHS2基因突变不是本研究南方汉族家族性SRNS家系的主要致病原因。
[Abstract]:Part I NPHS2 gene mutation analysis in children with sporadic steroid-resistant nephrotic syndrome in southern China objective to analyze the mutation and characteristics of NPHS2 gene in children with sporadic steroid-resistant nephrotic syndrome (steroid-resistantnephrotic syndrome,SRNS) in southern China. Methods 52 children with sporadic SRNS of Han nationality in southern China and 50 healthy volunteers with normal urine test were enrolled in the study. All exons of NPHS2 gene and some introns were amplified by genomic DNA;PCR from peripheral venous blood of all subjects, and the PCR products were sequenced by direct DNA sequencing. Results the heterozygous mutation of NPHS2 gene -148CT (R50W) was detected in a case of sporadic SRNS of Han nationality in southern China. The detection rate of NPHS2 gene heterozygosity was 1.9%. In addition, four reported polymorphisms of NPHS2 gene -102AGCT-288CT and 1038AGT were detected, and the frequencies of genotypes and alleles in 52 cases of SRNS were compared with those of 50 normal controls (P > 0.05). Conclusion there is a mutation of NPHS2 gene in children with sporadic SRNS of Han nationality in southern China, suggesting that NPHS2 gene mutation should be carried out in sporadic SRNS children of Han nationality in southern China. The second part: NPHS2 gene mutation analysis in the family of Chinese Han family with steroid-resistant nephrotic syndrome objective to analyze the mutation and characteristics of NPHS2 gene in the family of Chinese Han family with sex hormone resistant nephrotic syndrome (steroid-resistantnephrotic syndrome,SRNS). Methods the subjects of the study were proband, sister and parents of a Chinese Han familial SRNS family and 50 healthy volunteers with normal urine test. The whole exon of NPHS2 gene and its surrounding intron and promoter region were amplified by genomic DNA;PCR from peripheral venous blood of all subjects, and the PCR products were sequenced by direct DNA sequencing. Results the pathogenicity of 8 exons and peripheral introns and promoters of the NPHS2 gene was not detected in the proband in a Chinese Han familial SRNS pedigree in southern China. One mutation of -102AG (G34G) was detected in exon 1 of NPHS2 gene of proband, and three mutations were detected in promoter region of NPHS2 gene -1000AT-670CT and -537-531delCTTTT. These four NPHS2 gene mutations were detected in 50 normal controls and were known to be NPHS2 gene polymorphisms. Conclusion mutation of NPHS2 gene is not the main cause of familial SRNS in this study.
【学位授予单位】：福建医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R726.9

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