Identifying the genetic causality of familial IgAN by a new analysis system

通过新的分析系统识别家族性 IgAN 的遗传因果关系

• 批准号: 23659441
• 负责人: NARITA Ichiei
• 金额: $ 2.25万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23659441/
• 关键词: IgA腎症; ゲノム; 連鎖解析; 家族性; エクソーム解析; EEA1; SNP; 糖鎖不全; 慢性糸球体腎炎; 次世代シークエンサ

To identify the genetic causality of familial IgAN, we applied exome sequencing to a family comprising four biopsy-proven IgAN patients. Genome-wide linkage analysis was concurrently carried out. Thirteen variants which were shared only by affected individuals in the family were selected as candidate genes for familial IgAN. Linkage analysis of the family revealed linkage signals at nine loci, and among the candidates, a novel missense variant F161Y in EEA1, encoding Early Endosome Antigen 1. Furthermore, the F161Y variant completely co-segregated in the family and this variant is existed in the highly conserved region across zebrafish to human. Resequence analysis of EEA1 revealed that among additional 27 familial IgAN, six families carried the other three variants within EEA1. Frequencies of these EEA1 variants in familial IgAN was significantly higher than those in The Human Genetic Variation Database, indicating that EEA1 gene is a susceptibility gene for Japanese familial IgAN.

为了确定家族性IgAN的遗传因果关系，我们将外显子组测序应用于一个由四名活检证实的IgAN患者组成的家族。同时进行全基因组连锁分析。 13个变异体被选为家族性IgAN的候选基因，这些变异体仅在家族中受影响的个体中共享。该家族的连锁分析揭示了9个位点的连锁信号，在候选人中，EEA1中有一种新的错义变体F161 Y，编码早期内体抗原1。此外，F161 Y变异体在该家族中完全共分离，并且该变异体存在于从斑马鱼到人类的高度保守区域。EEA1的重测序分析显示，在另外27个家族性IgAN中，有6个家族携带EEA1内的其他3种变体。这些EEA1变异体在家族性IgAN中的频率显著高于人类遗传变异数据库中的频率，表明EEA1基因是日本家族性IgAN的易感基因。

项目成果

p.E66Q variant ofα-galactosidase A does not affect the progression of chronic kidney disease

α-半乳糖苷酶 A 的 p.E66Q 变体不影响慢性肾病的进展

• 发表时间: 2013
• 作者: Hirofumi Watanabe;Shin Goto;Hiroki Maruyama;Ichiei Narita
• 通讯作者: Ichiei Narita

Light-microscopic characteristics of IgG4-related tubulointerstitial nephritis: distinction from non-IgG4-related tubulointerstitial nephritis

• DOI: 10.1093/ndt/gfr761
• 发表时间: 2012-07-01
• 期刊: NEPHROLOGY DIALYSIS TRANSPLANTATION
• 影响因子: 6.1
• 作者: Yoshita, Kazuhiro;Kawano, Mitsuhiro;Saeki, Takako
• 通讯作者: Saeki, Takako

膜性増殖性糸球体腎炎Ｉ型,III型 新しい診断と治療のABC８０/腎８ネフローゼ症候群 2013年 最新医学 別冊

膜增生性肾小球肾炎I型和III型新诊断和治疗ABC80/Kidney 8肾病综合征2013年最新医疗补充

• 发表时间: 2013
• 作者: 金子佳賢;成田一衛 (今井 圓裕 編）
• 通讯作者: 成田一衛 (今井 圓裕 編）

AnnualReview腎臓2012

2012 年肾脏年度回顾

• 发表时间: 2012
• 作者: T. Konoshita;Y. Makino;T. Kimura;M. Fujii;S. Wakahara;K. Arakawa;I. Inoki;H. Nakamura;I. Miyamori I and the Genomic Disease Outcome Consortium (G-DOC) Study Investigators;横山仁
• 通讯作者: 横山仁

A hip fracture in a dialysis patient with Abeta2M amyloidosis

患有 Abeta2M 淀粉样变性的透析患者发生髋部骨折

• DOI: 10.1038/ki.2013.412
• 发表时间: 2014
• 期刊: Kidney International
• 影响因子: 19.6
• 作者: Kazama JJ;Yamamoto S;Wakasugi M;Narita I
• 通讯作者: Narita I