在未选择的卫生系统基础人群和COL4A5变异表型严重程度的基因型优先分析。

IF 10.3 1区医学 Q1 UROLOGY & NEPHROLOGY Journal of The American Society of Nephrology Pub Date : 2024-12-03 DOI:10.1681/ASN.0000000580

McKenzie Zellers, Kaushal Solanki, Melissa A Kelly, Karyn M Murphy, Kyle Retterer, H Lester Kirchner, Ion Dan Bucaloiu, Bryn Moore, Tooraj Mirshahi, Alexander R Chang

引用次数: 0

摘要

背景：我们对x连锁Alport综合征的了解主要来自于疾病更严重的选定队列。方法：我们采用基于基因型的方法，利用Geisinger MyCode discover研究的数据，研究了男性和女性x连锁阿尔波特综合征的表型谱，该研究是一项未选择的基于卫生系统的队列，具有外显子组测序和电子健康记录。根据社会人口统计学、糖尿病诊断和首次门诊就诊年份，将在ClinVar中报告为致病性或可能致病性COL4A5变异或蛋白截断变异的患者分别与多达5名没有COL4A3/4/5变异的对照进行匹配。检查的表型包括试纸血尿、双侧感音神经性听力损失、蛋白尿、肾小球滤过率降低和肾衰竭。结果：在170,856例患者中，有29例半合子男性（平均年龄52岁[SD 20]）和55例杂合子女性（平均年龄59岁[SD 19]）携带致病性/可能致病性COL4A5变异，其中48例携带半合子变异p.Gly624Asp。总体而言，非p的外显率（具有任何Alport综合征表型特征）最高。Gly624Asp变体（雄性：94%，雌性：85%），p.Gly624Asp的中间位点（雄性：77%，雌性：69%），与对照(雄性：32%；女性:50%)。男性肾衰竭的比例在非p。Gly624Asp变异（44%），雄性具有p.Gly624Asp变异（15%），雌性具有非p. asp变异（15%）。Gly624Asp变异（10%），与对照组（男性：3%，女性2%）相比。只有47%的COL4A5患者完成了蛋白尿筛查，少数患者正在服用肾素-血管紧张素醛固酮系统抑制剂。只有38%的男性和16%的女性被诊断为阿尔波特综合征或基底膜薄病。结论：使用基因型优先的方法，我们发现x连锁Alport综合征的男性和女性具有更高的相关表型特征风险，其严重程度范围比先前描述的更广，并且基因型具有可变性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

Genotype-First Analysis in an Unselected Health System-Based Population and Phenotypic Severity of COL4A5 Variants.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

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.

期刊最新文献

Testing Interventions that Address Kidney Health Disparities. Better Dialysis Care in the United States Requires New Payment Policy: No Patient Left Behind. Bundle Fix?: We Need an Act of Congress. Optimizing Quality Care within a Bundled Framework. Toward Noninvasive Biomarkers of Renal Senescence.