Gene Mapping for Familial Steroid Resistance Nephritic Syndrome

家族性类固醇抵抗性肾病综合征的基因定位

• 批准号: 16390245
• 负责人: TSUKAGUCHI Hiroyasu
• 金额: $ 8.77万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390245/
• 关键词: nephrotic syndrome; podocytes; mutation; linkage analysis

Familial steroid-resistant nephrotic syndrome (SRN) is characterized by early onset of proteinuria with rapid progression of renal failure and renal histology of focal segmental glomerulosclerosis (FSGS). Defects in genes encoding components of glomerular silt diaphragm, e.g., NPHS1, 2, and NEPH1, have been implicated in the pathogenesis. Even though NPHS1 and 2 mutations have been significantly involved in Caucasian families, the relevance in Asian counterparts remains unclear. To explore the genetic basis of Asian patients, we tested linkage of the 3 known nephrotic syndrome loci (NPHS1, 2, and NEPH1) in 15 recessive SRN families originating from Japan and Korea. Linkage analysis excluded the contribution of 3 genes in 32 out of total 45 samples (3 loci in 15 families). The other 13 samples (6 families at NPHS1, 4 at NPHS2, and 3 at NEPH1) were inconclusive on linkage analysis but direct-sequencing revealed no alterations, thereby excluding the loci in all 15 families. Our data underscored genetic heterogeneity and ethnic differences in the pathogenesis of FSGS, and suggests the presence of as yet unidentified genes in Asian patients.

家族性类固醇耐药肾病综合征（SRN）的特征是早期出现蛋白尿，并伴有肾功能衰竭的快速进展和局灶节段性肾小球硬化（FSGS）的肾组织学改变。编码肾小球淤泥质隔膜成分的基因缺陷，例如，NPHS1、2和NEPH1与发病机制有关。尽管NPHS1和NPHS2突变在高加索人家族中有显著的相关性，但在亚洲人中的相关性仍不清楚。为了探讨亚洲患者的遗传基础，我们在15个来自日本和韩国的隐性SRN家族中检测了3个已知的肾病综合征基因座（NPHS1，2和NEPH1）的连锁。连锁分析排除了32个样本（15个家系的3个位点）中3个基因的贡献。其他13个样本（6个家庭在NPHS1，4个在NPHS2，3个在NEPH1）的连锁分析是不确定的，但直接测序显示没有改变，从而排除了所有15个家庭的基因座。我们的数据强调了FSGS发病机制的遗传异质性和种族差异，并提示亚洲患者中存在尚未鉴定的基因。

项目成果

Annual Review 腎臓2006 一過性ネフローゼ症候群発症の分子病態

2006 年肾脏年度回顾 短暂性肾病综合征发病的分子发病机制

• 发表时间: 2005
• 作者: Asoh S;et al.;塚口 裕康
• 通讯作者: 塚口 裕康

Raft-Dependent Endocytic Pathway of Nephrin Down-regulates Its Signal Transduction Through interaction with Src-Family Kinase Fyn.

Nephrin 的筏依赖性内吞途径通过与 Src 家族激酶 Fyn 相互作用下调其信号转导。

• 发表时间: 2005
• 期刊: J Am Soc Nephrol 16
• 作者: Shono A;Tsukaguchi H;X-S Qin;Doi T.
• 通讯作者: Doi T.

Annual Review 腎臓 2006 一過性ネフローゼ症候群発症の分子病態

2006 年肾脏年度回顾 短暂性肾病综合征发病的分子发病机制

• 发表时间: 2005
• 作者: Asoh S;et al.;塚口 裕康;塚口 裕康
• 通讯作者: 塚口 裕康

Genetic Scanning for 12 Asian Families with Steroid Resistant Nephrotic Syndrome(SRN) Based on Haplotype Analysis and Computer Simulation Approach

基于单倍型分析和计算机模拟方法对 12 个亚洲类固醇抵抗性肾病综合征 (SRN) 家系进行基因扫描

• 发表时间: 2004
• 期刊: J Am Soc Nephrol 15
• 作者: Katsura KI;et al.;Kitamura A et al.
• 通讯作者: Kitamura A et al.

Molecular Mechanism for Proteinuria in Recurrent Nephrotic Syndrome.

复发性肾病综合征蛋白尿的分子机制。

• 发表时间: 2006
• 期刊: Annual Review 2006 Kidney (Chugai Igaku (Tokyo)) 74-80
• 作者: Tsukaguchi H;Iijima K.
• 通讯作者: Iijima K.