PDF(Pubmed)
Abstract：
UNASSIGNED: Genetic testing is increasingly utilized in nephrology practice, but limited real-world data exist on variant reclassification following renal genetics testing.
UNASSIGNED: A cohort of patients at the Cleveland Clinic Renal Genetics Clinic who underwent genetic testing through clinical laboratories was assessed with their clinical and laboratory data analyzed.
UNASSIGNED: Between January 2019 and June 2023, 425 new patients with variable kidney disorders from 413 pedigrees completed genetic testing through 10 clinical laboratories, including 255 (60%) females with median (25th, 75th percentiles) age of 36 (22-54) years. Multigene panel was the most frequently used modality followed by single-gene testing, exome sequencing (ES), chromosomal microarray (CMA), and genome sequencing (GS). At initial report, 52% of patients had ≥1 variants of uncertain significance (VUS) with or without concurrent pathogenic variant(s). Twenty amendments were issued across 19 pedigrees involving 19 variants in 17 genes. The overall variant reclassification rate was 5%, with 63% being upgrades and 32% downgrades. Of the reclassified variants, 79% were initially reported as VUS. The median time-to-amendments from initial reports was 8.4 (4-27) months. Following the variant reclassifications, 60% of the patients received a new diagnosis or a change in diagnosis. Among these, 67% of patients received significant changes in clinical management.
UNASSIGNED: Variant reclassification following genetic testing is infrequent but important for diagnosis and management of patients with suspected genetic kidney disease. The majority of variant reclassifications involve VUS and are upgrades in clinically issued amended reports. Further studies are needed to investigate the predictors of such events.
UNASSIGNED: A cohort of patients at the Cleveland Clinic Renal Genetics Clinic who underwent genetic testing through clinical laboratories was assessed with their clinical and laboratory data analyzed.
UNASSIGNED: Between January 2019 and June 2023, 425 new patients with variable kidney disorders from 413 pedigrees completed genetic testing through 10 clinical laboratories, including 255 (60%) females with median (25th, 75th percentiles) age of 36 (22-54) years. Multigene panel was the most frequently used modality followed by single-gene testing, exome sequencing (ES), chromosomal microarray (CMA), and genome sequencing (GS). At initial report, 52% of patients had ≥1 variants of uncertain significance (VUS) with or without concurrent pathogenic variant(s). Twenty amendments were issued across 19 pedigrees involving 19 variants in 17 genes. The overall variant reclassification rate was 5%, with 63% being upgrades and 32% downgrades. Of the reclassified variants, 79% were initially reported as VUS. The median time-to-amendments from initial reports was 8.4 (4-27) months. Following the variant reclassifications, 60% of the patients received a new diagnosis or a change in diagnosis. Among these, 67% of patients received significant changes in clinical management.
UNASSIGNED: Variant reclassification following genetic testing is infrequent but important for diagnosis and management of patients with suspected genetic kidney disease. The majority of variant reclassifications involve VUS and are upgrades in clinically issued amended reports. Further studies are needed to investigate the predictors of such events.
摘要：
■基因检测越来越多地用于肾病学实践，但关于肾遗传学检测后变异再分类的真实数据有限。
■克利夫兰诊所肾脏遗传学诊所的一组患者通过临床实验室进行基因检测，并对他们的临床和实验室数据进行分析。
■在2019年1月至2023年6月之间，来自413个家系的425名新的肾脏疾病患者通过10个临床实验室完成了基因检测，包括255名(60%)女性，中位数(第25位，第75百分位数）年龄36（22-54）岁。多基因面板是最常用的模式，其次是单基因测试，外显子组测序（ES），染色体微阵列（CMA），和基因组测序（GS）。在初次报告中,52％的患者有≥1个不确定意义的变异（VUS），有或没有并发致病性变异。在19个谱系中发布了20个修正案，涉及17个基因中的19个变体。总体变异体重分类率为5%，63%是升级，32%是降级。在重新分类的变体中，79%最初报告为VUS。初次报告的修改时间中位数为8.4（4-27）个月。在变体重新分类之后，60％的患者获得了新的诊断或诊断改变。其中,67%的患者接受了临床管理的显著改变。
基因检测后的变异重新分类很少见，但对疑似遗传性肾病患者的诊断和治疗很重要。大多数变体重新分类涉及VUS，并且是临床发布的修订报告中的升级。需要进一步的研究来调查此类事件的预测因素。
■克利夫兰诊所肾脏遗传学诊所的一组患者通过临床实验室进行基因检测，并对他们的临床和实验室数据进行分析。
■在2019年1月至2023年6月之间，来自413个家系的425名新的肾脏疾病患者通过10个临床实验室完成了基因检测，包括255名(60%)女性，中位数(第25位，第75百分位数）年龄36（22-54）岁。多基因面板是最常用的模式，其次是单基因测试，外显子组测序（ES），染色体微阵列（CMA），和基因组测序（GS）。在初次报告中,52％的患者有≥1个不确定意义的变异（VUS），有或没有并发致病性变异。在19个谱系中发布了20个修正案，涉及17个基因中的19个变体。总体变异体重分类率为5%，63%是升级，32%是降级。在重新分类的变体中，79%最初报告为VUS。初次报告的修改时间中位数为8.4（4-27）个月。在变体重新分类之后，60％的患者获得了新的诊断或诊断改变。其中,67%的患者接受了临床管理的显著改变。
基因检测后的变异重新分类很少见，但对疑似遗传性肾病患者的诊断和治疗很重要。大多数变体重新分类涉及VUS，并且是临床发布的修订报告中的升级。需要进一步的研究来调查此类事件的预测因素。
