Targeted Next-Generation Sequencing Identifies Pathogenic Variants in Diabetic Kidney Disease

作者：José M. Lázaro-Guevara, Julio C. Fierro Morales, Alice Wright, River Gunville, Christopher A. Simeone, Scott G. Frodsham, Melissa H. Pezzolesi, Courtney A. Zaffino, Laith Al‐Rabadi, Nirupama Ramkumar, Marcus G. Pezzolesi · 发表于：American Journal of Nephrology · 年份：2021 · DOI：10.1159/000514578 · 被引用次数：9 · 研究领域：Chronic Kidney Disease and Diabetes、Renal Diseases and Glomerulopathies、Genetic Associations and Epidemiology

INTRODUCTION: 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. METHODS: Here, we set out to investigate the genetic basis of disease in nondiabetic kidney disease (NDKD) and diabetic kidney disease (DKD) patients by performing targeted NGS using a custom panel comprising 345 kidney disease-related genes. RESULTS: 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. DISCUSSION/CONCLUSION: 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.