家族性局灶节段肾小球硬化症一家系临床与基因调查

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。

A familial focal segmental glomerulosclerosis Chinese kindred

Objective:To investigate the clinic features of a familial focal segmental glomerulosclerosis(FFSGS)kindred,and screen three already known pathogenic genes of FFSGS.Methodology:A Chinese FSGS family was investigated.78 members in this family were screened.Then further clinic examinations were taken for the part of suspected ones.The peripheral blood samples of 67 members were taken and genomic DNA was extracted.Polymerase chain reaction was used to amplify all the extrons of NPHS2.ACTN4 and TRPC6,which are associated with FFSGS.The products were purified and then sequenced to determine whether any mutation was existed.Results:The family was comprised of fourgeneration,and 103 members which was the largest FSGS kindred reported in china.It is an autosomal dominant inherited FSGS kindred.At Jeast 11 members were affected.All of them showed late-onset with a mean age of 35.9 years old on presentation and proteinuria in different level.Two had renal biopsy proven FSGS and six also complicated with microscopy hematuria.The clinic manifestations and prognosis were different among the patients in the kindred.All the extrons of NPHS2,ACTN4 and TRPC6 were successfully amplified.No mutation was found after careful examination,while seven SNPs were found.Conclusion:The family was the largest late-onset.autosomal dominant inherited Chinese FSGS kindred.Patients in this family showed different clinic manifestations and prognosis.The already known pathogenic gene NPHS2.ACTN4 and TRPC6 were not the disease-causing genes for this family.