School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Stephen's Green, Dublin, Ireland D02 YN77.
Department of Nephrology and Transplantation, Beaumont Hospital, Dublin 9, Ireland D09 V2N0.
Cold Spring Harb Mol Case Stud. 2020 Oct 7;6(5). doi: 10.1101/mcs.a005462. Print 2020 Oct.
High-throughput DNA testing is becoming established as a standard diagnostic test in the renal clinic. Previously published studies on cohorts of patients with unexplained chronic kidney disease of a suspected genetic aetiology have suggested a diagnostic yield for genomic sequencing of up to 18%. Here we determine the yield of targeted gene panel in a clinically unscreened cohort of patients referred for percutaneous native renal biopsy. Patients who underwent renal biopsy for investigation of chronic kidney disease were sequenced using a genomic sequencing panel covering 227 genes in which variation is known to be associated with monogenic chronic kidney disease (CKD). Candidate disease-causing variants were assessed for pathogenicity using guidelines from the American College for Medical Genetics and Genomics. Fifty CKD patients were recruited and sequenced. A molecular diagnosis was obtained for two patients (4%). A molecular diagnosis is possible using genomic testing in ∼4% of clinically unscreened patients undergoing renal biopsy. Genetic screening may be useful for diagnosis in a subset of CKD patients but is most valuable when applied to patients with suspected heritable forms of kidney disease.
高通量 DNA 检测已成为肾脏临床的标准诊断检测方法。先前发表的针对疑似遗传病因不明的慢性肾脏病患者队列的研究表明，基因组测序的诊断率高达 18%。在这里，我们确定了在未经临床筛查的接受经皮肾活检的患者队列中，靶向基因 panel 的检出率。对因慢性肾脏病而接受肾活检的患者进行了基因测序，使用了一个包含 227 个基因的基因组测序 panel，这些基因的变异已知与单基因慢性肾脏病 (CKD) 相关。使用美国医学遗传学和基因组学学院的指南评估候选致病变异的致病性。招募了 50 名 CKD 患者并进行了测序。两名患者（4%）获得了分子诊断。在接受肾活检的未经临床筛查的患者中，约有 4%可以通过基因组检测获得分子诊断。基因筛查对某些 CKD 患者的诊断可能有用，但在应用于疑似遗传性肾脏疾病患者时最有价值。
