Understanding the clinical genetics of kidney stone disease using the Natera Renasight panel.

IF 2 2区 医学 Q2 UROLOGY & NEPHROLOGY
Andrewe L Baca, Rutul D Patel, Kevin Labagnara, Benjamin Green, Michael Zhu, Kavita Gupta, Beth Edelblute, Andrea A Asencio, Deep Sharma, Wei Chen, Dima Raskolnikov, Jillian Donnelly, Kara L Watts, Alexander C Small
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Abstract

We aimed to characterize the underlying genetics of kidney stone disease (KSD) in an urban and diverse population using the Natera Renasight genetic panel. This was a single-center prospective study of high-risk KSD patients, defined as recurrent stone formers or those with a family history with KSD. Buccal saliva DNA samples were collected with the commercially available Natera Renasight genetic panel and were analyzed using next-generation sequencing. The panel assesses 385 kidney disease related genes, including 45 linked to KSD. One hundred eleven high-risk KSD patients were enrolled. The majority were female (56%) with a median age of 50 (IQR 39.5-59.5), compromising a diverse ethnic background with 62% Hispanic, 23% White and 11% Black. Patients had median 3 (IQR 2-5) lifetime stone episodes, and 41% had family history of KSD. Genetic analysis was possible for 105 patients (95%). Eight (8%) had positive tests with only one patient found to have a pathogenic mutation associated with KSD (SLC7A9, cystinuria). The other 7 positive tests included amyloidosis (TTR, N = 3), Alport syndrome (COL4A3, N = 2), polycystic kidney disease (PKD1, N = 1), and susceptibility to ESRD (APOL1, N = 1). Patients with positive tests were more likely to have chronic kidney disease (38% vs 5%, p < 0.01), gout (13% vs 1%, p = 0.02) and carbonate apatite stones (38% vs 7%, p < 0.01). Our study sheds light on genetic factors of KSD in a diverse patient population. The results suggest that KSD is unlikely monogenetic in nature, but is more likely due to a complex interplay of polygenetic and environmental influences. Genetic testing may be most useful in KSD patients with chronic kidney disease.

使用 Natera Renasight 面板了解肾结石病的临床遗传学。
我们的目的是利用Natera Renasight基因面板在城市和不同人群中表征肾结石疾病(KSD)的潜在遗传学。这是一项针对高风险KSD患者的单中心前瞻性研究,定义为复发性结石患者或有KSD家族史的患者。使用市售的Natera Renasight基因板收集口腔唾液DNA样本,并使用下一代测序进行分析。该小组评估了385个肾脏疾病相关基因,包括45个与KSD相关的基因。111例高危KSD患者入组。大多数是女性(56%),中位年龄为50岁(IQR 39.5-59.5),种族背景多样,其中西班牙裔占62%,白人占23%,黑人占11%。患者一生中平均有3次(IQR 2-5)结石发作,41%有KSD家族史。105例(95%)患者可进行遗传分析。8例(8%)检测呈阳性,只有1例患者发现有与KSD相关的致病突变(SLC7A9,胱氨酸尿)。其他7项阳性检测包括淀粉样变性(TTR, N = 3)、Alport综合征(COL4A3, N = 2)、多囊肾病(PKD1, N = 1)和ESRD易感性(APOL1, N = 1)。检测结果呈阳性的患者更有可能患有慢性肾脏疾病(38% vs 5%, p
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来源期刊
Urolithiasis
Urolithiasis UROLOGY & NEPHROLOGY-
CiteScore
4.50
自引率
6.50%
发文量
74
期刊介绍: Official Journal of the International Urolithiasis Society The journal aims to publish original articles in the fields of clinical and experimental investigation only within the sphere of urolithiasis and its related areas of research. The journal covers all aspects of urolithiasis research including the diagnosis, epidemiology, pathogenesis, genetics, clinical biochemistry, open and non-invasive surgical intervention, nephrological investigation, chemistry and prophylaxis of the disorder. The Editor welcomes contributions on topics of interest to urologists, nephrologists, radiologists, clinical biochemists, epidemiologists, nutritionists, basic scientists and nurses working in that field. Contributions may be submitted as full-length articles or as rapid communications in the form of Letters to the Editor. Articles should be original and should contain important new findings from carefully conducted studies designed to produce statistically significant data. Please note that we no longer publish articles classified as Case Reports. Editorials and review articles may be published by invitation from the Editorial Board. All submissions are peer-reviewed. Through an electronic system for the submission and review of manuscripts, the Editor and Associate Editors aim to make publication accessible as quickly as possible to a large number of readers throughout the world.
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