一种新的单基ALG5变体导致晚期发病的ADPKD和管间纤维化
Elhussein A E Elhassan1,2, Tereza Kmochová3, Katherine A Benson4
1Department of Nephrology and Transplantation, Beaumont Hospital, Dublin, Ireland.
Kidney international reports
|July 31, 2024
概括
一种新的ALG5基因变异,p.R79W,通过扰乱尿素成熟,导致晚发性自体主导多囊性病 (ADPKD). 这项研究揭示了ALG5在ADPKD病原和损伤中的作用.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 腎臟病學 (nephrology) 是一種醫學專業.
背景情况:
- ALG5基因中的单变异会导致一种自体主导的多囊性病样 (ADPKD样) 现型.
- ALG5 功能障碍导致低糖化,扰乱了多素-1 (PC1) 的成熟和贩运.
- 一种新的ALG5变体,p.R79W,在非典型的晚发性ADPKD和管间损伤的家庭中被确定.
研究的目的:
- 调查ALG5新型变异 (p.R79W) 的临床,遗传和分子相关性,在两家爱尔兰晚期发病ADPKD的家庭中.
- 阐明ALG5相关脏疾病背后的致病机制.
- 探索ALG5变异对蛋白质糖化和ADPKD贩运的影响.
主要方法:
- 整体外体和针对性测序用于遗传分离分析.
- 细胞活检的免疫组织化学,以评估蛋白质局部化.
- 血和尿液蛋白质和N-糖质研究,包括针对性分析UMOD和MUC1.
主要成果:
- 一个单基ALG5变体 (p.R79W) 与23名 (18名受影响) 个体的疾病共分离.
- 在患者的细胞中观察到Golgi中异常的ALG5局部化和ER中尿模素的病态积累.
- 在受影响的个体中检测到血和尿液中泌尿激素水平的降低以及CKD相关蛋白质的失调.
结论:
- ALG5功能障碍会影响N-糖化和GPI定蛋白质的成熟和贩运,尤其是尿模素.
- 这导致脏结构和功能变化,证实ALG5是晚发ADPKD的原因.
- 这项研究更深入地了解了与ALG5变异相关的ADPKD分子机制.
更多相关视频
07:35Use of Ultra-high Field MRI in Small Rodent Models of Polycystic Kidney Disease for In Vivo Phenotyping and Drug Monitoring
Published on: June 23, 2015
11.5K
08:46Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium
Published on: September 1, 2015
9.8K
相关概念视频
02:41Lethal Alleles
15.4K
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
15.4K
01:33Pleiotropy
40.4K
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
40.4K
03:14Notch Signaling Pathway
4.2K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.2K