The Importance of Copy Number Variant Analysis in Patients with Monogenic Kidney Disease

被引:1
作者
Claus, Laura R. [1 ]
Ernst, Robert F. [1 ]
Elferink, Martin G. [1 ]
van Deutekom, Hanneke W. M. [1 ]
van der Zwaag, Bert [1 ]
van Eerde, Albertien M. [1 ]
机构
[1] Univ Med Ctr Utrecht, Dept Genet, KC-04-084-2,POB 85090, NL-3508 AB Utrecht, Netherlands
来源
KIDNEY INTERNATIONAL REPORTS | 2024年 / 9卷 / 09期
关键词
CNV analysis; diagnostic yield; ExomeDepth; genetic testing; nephrogenetics; JOINT CONSENSUS RECOMMENDATION; MEDICAL GENETICS; AMERICAN-COLLEGE; ASSOCIATION; STANDARDS; GENOMICS;
D O I
10.1016/j.ekir.2024.06.026
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Introduction: Genetic testing can reveal monogenic causes of kidney diseases, offering diagnostic, therapeutic, and prognostic benefits. Although single nucleotide variants (SNVs) and copy number variants (CNVs) can result in kidney disease, CNV analysis is not always included in genetic testing. Methods: We investigated the diagnostic value of CNV analysis in 2432 patients with kidney disease genetically tested at the University Medical Centre Utrecht between 2014 and May 2022. We combined previous diagnostic testing results, encompassing SNVs and CNVs, with newly acquired results based on retrospective CNV analysis. The reported yield considers both the American College of Medical Genetics and Genomics (ACMG) classification and whether the genotype actually results in disease. Results: We report a diagnostic yield of at least 23% for our complete diagnostic cohort. The total diagnostic yield based solely on CNVs was 2.4%. The overall contribution of CNV analysis, defined as the proportion of positive genetic tests requiring CNV analysis, was 10.5% and varied among different disease subcategories, with the highest impact seen in congenital anomalies of the kidney and urinary tract (CAKUT) and chronic kidney disease at a young age. We highlight the efficiency of exome-based CNV calling, which reduces the need for additional diagnostic tests. Furthermore, a complex structural variant, likely a COL4A4 founder variant, was identified. Additional findings unrelated to kidney diseases were reported in a small percentage of cases. Conclusion: In summary, this study demonstrates the substantial diagnostic value of CNV analysis, providing insights into its contribution to the diagnostic yield and advocating for its routine inclusion in genetic testing of patients with kidney disease.
引用
收藏
页码:2695 / 2704
页数:10
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