Whole exome analysis for causative genes of familial IgA nephropathy

在散发性伊加肾病（IgAN）中，GWAS揭示了几种风险变体，然而，家族性IgAN的致病基因仍然难以捉摸。我们应用外显子组测序分析在家庭包括四个活检证实的IgA肾病。为了确定致病基因变异，根据非同义、频率低于1000个基因组计划的1%和符合常染色体显性遗传的杂合性进行了多次筛选。最后，选择了所有受影响个体共有的13个变体。其中，EEA1变异体与家族成员的患病状态完全共分离，在序列保守性和氨基酸替换预测蛋白质功能变化方面显示出显著较高的价值。我们现在正在研究EEA1变体的功能分析，预计这些分析将导致创新疗法的发展。

In sporadic IgA nephropathy (IgAN), GWAS disclosed several risk variants, however, causative genes for familial IgAN remained elusive. We applied exome sequencing analysis in family comprising of four biopsy-proven IgAN. To identify the causative gene variant, several filtering screening were carried out based on non-synonymous, frequency less than one percent of 1000 genome project, and heterozygosity fitted with autosomal dominant inheritance. Finally, 13 variants were selected shared by all affected individuals. Among them, EEA1 variant were completely cosegregated with affection status of the family members, showed significant higher values in sequence conservation and prediction of functional changes of protein by amino-acid substitution. We are now investigating the functional analysis of EEA1 variant, and it is expected that these analyses will lead to the development of innovative therapeutics.