TRPC6相关荚膜细胞病的自然史和临床病理关联

IF 10.3 1区 医学 Q1 UROLOGY & NEPHROLOGY
Benjamin Wooden, Andrew Beenken, Elena Martinelli, Ken Saida, Andrea L Knob, Juntao Ke, Isabella Pisani, Gina Jin, Brandon Lane, Adele Mitrotti, Elizabeth Colby, Tze Y Lim, Francesca Guglielmi, Amy J Osborne, Dina F Ahram, Chen Wang, Farid Armand, Francesca Zanoni, Andrew S Bomback, Marco Delsante, Gerald B Appel, Massimo R A Ferrari, Jeremiah Martino, Sunil Sahdeo, David Breckenridge, Slavé Petrovski, Dirk S Paul, Gentzon Hall, Riccardo Magistroni, Corrado Murtas, Sandro Feriozzi, Teresa Rampino, Pasquale Esposito, Margaret E Helmuth, Matthew G Sampson, Matthias Kretzler, Krzysztof Kiryluk, Shirlee Shril, Loreto Gesualdo, Umberto Maggiore, Enrico Fiaccadori, Rasheed Gbadegesin, Dominick Santoriello, Vivette D D'Agati, Moin A Saleem, Ali G Gharavi, Friedhelm Hildebrandt, Martin R Pollak, David B Goldstein, Simone Sanna-Cherchi
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引用次数: 0

摘要

背景:了解人类疾病的遗传基础已成为药物开发和精准医疗不可或缺的一部分。最近的研究进展使人们能够确定驱动疾病的分子通路,从而制定有针对性的治疗策略。生物技术行业对罕见病的投资不断增加,这凸显了基因证据在药物发现和审批过程中的重要性。在此,我们研究了一种单基因孟德尔肾病--TRPC6相关荚膜细胞病(TRPC6-AP),在一大批TRPC6因果变异患者中展示其自然史、遗传谱和临床病理关联,以帮助明确疾病的具体特征,进一步促进药物开发和临床试验设计。从国内外多个中心收集了临床数据,包括发病年龄、实验室结果、治疗反应、肾活检结果和遗传信息。进行了外显子组或靶向测序,并根据严格的标准进行了变异分类。对 TRPC6 变体进行了结构和功能分析,以了解它们对蛋白质功能的影响。对 9 例肾脏活检的光镜和电子显微镜标本进行了深入的再分析,以确定 TRPC6-AP 的病理特征和相关性:大规模测序数据不支持TRPC6蛋白截断变异的因果关系。我们发现了21个独特的TRPC6错义变异,它们聚集在蛋白质的三个不同区域,对TRPC6三维蛋白质结构有不同的影响。肾活检分析表明,大多数病例都存在 FSGS 损伤模式,荚膜细胞特征明显,包括弥漫性足突脱出和细胞体肿胀。大多数患者在青春期或成年早期发病,但变化很大(平均 22 岁,SD ± 14 岁),经常发展为肾衰竭,但发病与 ESKD 之间的时间存在差异:本研究有助于深入了解 TRPC6-AP 的遗传谱、临床病理关联和自然史。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Natural History and Clinicopathological Associations of TRPC6-Associated Podocytopathy.
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来源期刊
Journal of The American Society of Nephrology
Journal of The American Society of Nephrology 医学-泌尿学与肾脏学
CiteScore
22.40
自引率
2.90%
发文量
492
审稿时长
3-8 weeks
期刊介绍: The Journal of the American Society of Nephrology (JASN) stands as the preeminent kidney journal globally, offering an exceptional synthesis of cutting-edge basic research, clinical epidemiology, meta-analysis, and relevant editorial content. Representing a comprehensive resource, JASN encompasses clinical research, editorials distilling key findings, perspectives, and timely reviews. Editorials are skillfully crafted to elucidate the essential insights of the parent article, while JASN actively encourages the submission of Letters to the Editor discussing recently published articles. The reviews featured in JASN are consistently erudite and comprehensive, providing thorough coverage of respective fields. Since its inception in July 1990, JASN has been a monthly publication. JASN publishes original research reports and editorial content across a spectrum of basic and clinical science relevant to the broad discipline of nephrology. Topics covered include renal cell biology, developmental biology of the kidney, genetics of kidney disease, cell and transport physiology, hemodynamics and vascular regulation, mechanisms of blood pressure regulation, renal immunology, kidney pathology, pathophysiology of kidney diseases, nephrolithiasis, clinical nephrology (including dialysis and transplantation), and hypertension. Furthermore, articles addressing healthcare policy and care delivery issues relevant to nephrology are warmly welcomed.
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