Targeted Next-Generation Sequencing Identifies Pathogenic Variants in Diabetic Kidney Disease.
Targeted Next-Generation Sequencing Identifies Pathogenic Variants in Diabetic Kidney Disease.
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DOI：
10.1159/000514578
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发表时间：
2021
影响因子：
4.2
通讯作者：
Pezzolesi MG
中科院分区：
文献类型：
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作者：
Lazaro-Guevara J;Fierro-Morales J;Wright AH;Gunville R;Simeone C;Frodsham SG;Pezzolesi MH;Zaffino CA;Al-Rabadi L;Ramkumar N;Pezzolesi MG
糖尿病是慢性肾脏疾病（CKD）最常见的病因。对于患有糖尿病和CKD的患者，他们肾脏疾病的潜在原因通常被认为是糖尿病的后果。然而，在没有组织病理学证实的情况下，他们疾病的根本原因尚不清楚。最近的研究表明，下一代测序（NGS）为揭示和建立各种肾脏疾病的精确遗传诊断提供了一条有希望的途径。在这里，我们开始研究非糖尿病肾病（NDKD）和糖尿病肾病（DKD）患者疾病的遗传基础，通过使用由345个肾脏疾病相关基因组成的定制面板进行靶向NGS。我们的分析发现了基于ACMG-AMP指南的罕见诊断变异，这些变异与本研究中19%的NDKD患者的临床诊断一致。同样，22%的DKD患者在我们的研究小组中发现携带肾脏疾病相关基因的罕见致病性/可能致病性变异。在本研究纳入的3%的糖尿病患者中检测到提示NDKD的遗传变异。我们的研究结果表明，糖尿病背景下肾脏疾病相关基因的罕见变异可能在糖尿病患者DKD和NDKD的发病机制中发挥作用。
Diabetes is the most common cause of chronic kidney disease (CKD). For patients with diabetes and CKD, the underlying cause of their kidney disease is often assumed to be a consequence of their diabetes. Without histopathological confirmation, however, the underlying cause of their disease is unclear. Recent studies have shown that next-generation sequencing (NGS) provides a promising avenue toward uncovering and establishing precise genetic diagnoses in various forms of kidney disease. Here, we set out to investigate the genetic basis of disease in non-diabetic kidney disease (NDKD) and diabetic kidney disease (DKD) patients by performing targeted NGS using a custom panel comprised of 345 kidney disease-related genes. Our analysis identified rare diagnostic variants based on ACMG-AMP guidelines that were consistent with the clinical diagnosis of 19% of the NDKD patients included in this study. Similarly, 22% of DKD patients were found to carry rare pathogenic/likely pathogenic variants in kidney disease-related genes included on our panel. Genetic variants suggestive of NDKD were detected in 3% of the diabetic patients included in this study. Our findings suggest that rare variants in kidney disease-related genes in a diabetic background may play a role in the pathogenesis of DKD and NDKD in patients with diabetes.