家族性局灶节段性肾小球硬化一家系相关基因连锁分析

目的 对1个家族性局灶节段性肾小球硬化（FFSGS）家系的临床表型进行连锁分析，并对国内外已知的4个基因进行排除性定位。 方法 调查该家系成员的临床资料。应用两点连锁分析方法，在已知的FFSGS遗传的相关基因WT1、TRPC6、CD2AP、NPHS2所在染色体区域，选取9个微卫星遗传标记（STR）进行连锁分析。 结果 该FFSGS家系的遗传方式为常染色体显性遗传。19名家系成员中1例已进展至终末期肾病（ESRD）；4例尿检异常成员中2例病理明确诊断为FSGS；Ⅲ9和Ⅲ15患者发病年龄较早，分别为10岁和13岁；第Ⅰ和第Ⅱ代的患者均为25岁以后发病。用D1S196、D1S218、D1S238、11S935、D11S898、D11S908、D11S1986、D6S936、D6S1566等9个STR对该家系进行NPHS2、CD2AP、TRPC6和WT1基因的两点连锁分析，测得各个标记位点在重组率θ=0时，最大优势对数（LOD） 值为0.32 (D11S1986)，不支持连锁。 结论 该FFSGS家系遗传方式为常染色体显性遗传。已知基因NPHS2、WT1、TRPC6、CD2AP不是该家系的致病基因。

Linkage analysis of associated genes in a Chinese kindred of familial focal segmental glomerulosclerosis

Objective To perform the exclusive gene mapping around four known genes associated with familial focal segmental glomerulosclerosis(FFSGS)in a FFSGS kindred using linkage analysis.Methods The clinical features of available members in this kindred were investigated.Nine microsatellite markers around WT1,TRPC6,CD2AP and NPHS2 loci were selected and applied to analyze the linkage in the available family members.By two-point linkage analysis and allele sharing analysis,exclusive gene mapping on NPHS2,WT1,TRPC6 and CD2AP were carried out in this FFSGS kindred.Results Autosomal dominant inheritance pattern was demonstrated in phenotypes of this family.Of 19 family members,1 suffered from end-stage renal disease(ESRD),4 individuals were found to have proteinuria,and 2 affected individuals underwent renal biopsy and were diagnosed as FSGS.The youngest age of onset was 10 years old.This autosomal dominant FSGS was evaluated for linkage using microsatellite markers including D1S196,D1S218,D1S238,D11S935,D11S898,D11S908,D11S1986,D6S936,D6S1566 and so on.The maximal two-point logarithm of odds(LOD)score was 0.32 at θ=0 in marker D11S1986.These markers were not cosegregated with the disease loci in all the affected members,which indicated that there was no linkage between these markers and four FFSGS related genes(CD2AP,WT1,NPHS2 and TPdPC6)in the kindred.Conclusions The inheritance pattern of this kindred is autosomal dominant.NPHS2,WT1,TRPC6 and CD2AP are not the disease-causing genes for this family.