论文部分内容阅读
目的:分析一个局灶节段性肾小球硬化症(FSGS)家系的临床特征,并对已知致病基因进行筛查。方法:调查1个中国汉族人FSGS家系,筛查其中78名成员后对可疑成员进行仔细临床检查。采集家系中67名成员的外周血样抽提基因组DNA,采用PCR扩增先证者NPHS2,ACTN4和TRPC6基因的所有外显子,寻找突变的方法对已知的家族性FSGS致病基因进行筛查。结果:该家系共有4代,103名成员,遗传方式为常染色体显性遗传。78名被调查家系成员中有11例患者和3例疑似患者迟发起病,平均发病年龄35.9岁。两例患者经肾活检证实为FSGS,其余患者均有不同程度蛋白尿,部分伴镜下血尿。家系先证者基因组DNA进行PCR逐个外显子扩增测序,未发现NPHS2、ACTN4、TRPC6三个已知的致病基因存在突变,发现SNP7个。结论:本家系是已报道最大的一个中国汉族人FSGS家系,符合常染色体显性遗传迟发起病型,家系内患者间临床表现存在明显差异。已知基因NPHS2、ACTN4、TRPC6不是该家系的致病基因。
OBJECTIVE: To analyze the clinical features of a pedigree of focal segmental glomerulosclerosis (FSGS) and to screen for known causative genes. Methods: A Chinese Han FSGS pedigree was investigated and 78 members were screened for careful clinical examination of suspicious individuals. Genomic DNA was extracted from peripheral blood samples of 67 members of the pedigree, and all exons of NPHS2, ACTN4 and TRPC6 genes of probands were amplified by PCR to search for mutations. The known familial FSGS pathogenic genes were screened . Results: There were 4 generations and 103 members in this pedigree. The inheritance mode was autosomal dominant. Of the 78 surveyed family members, 11 patients and 3 suspected patients were late onset with an average age of 35.9 years. Two patients confirmed by the renal biopsy FSGS, the rest of patients with varying degrees of proteinuria, some accompanied by microscopic hematuria. Family proband genomic DNA by PCR exome sequencing, found no NPHS2, ACTN4, TRPC6 three known pathogenicity mutations exist, found 7 SNPs. CONCLUSION: This pedigree is the most reported Chinese FSGS pedigree in Han Chinese, which is consistent with autosomal dominant onset. The clinical manifestations among pedigrees are obviously different. Known genes NPHS2, ACTN4, TRPC6 is not the causative gene of the family.