Kirwin Susan M, Robbins Katherine M, Vinette Kathleen M B, Hirata Lee, Gripp Karen W, Funanage Vicky L
Nemours Children's Health, Molecular Diagnostics Laboratory.
Dela J Public Health. 2021 Dec 15;7(5):24-27. doi: 10.32481/djph.2021.12.008. eCollection 2021 Dec.
Chronic kidney disease (CKD) has major morbidity and mortality for children and adults. While in adults CKD often is associated with diabetic complications, genetic variants can be the underlying cause in both populations. Beginning in 2016 with the emergence of more affordable next-generation sequencing (NGS) technologies, the Molecular Diagnostics Lab at Nemours Children's Hospital-Delaware developed the first clinically actionable pediatric NGS kidney panel comprised of 46 genes including . Apolipoprotein L1 () associated nephropathy is reported along a spectrum of non-diabetic kidney disease. It is significantly associated with two "risk alleles" defined as G1 and G2 and typically found in individuals of African descent. In early 2020, as COVID-19 spread across the globe, reports of patients with kidney failure began to emerge. A collapsing glomerulopathy in Black patients with COVID-19 was found to be associated with the predisposition of the known G1 and/or G2 risk variants. We identified genetic variants in 11 genes () known to be associated with pediatric onset nephrotic syndrome, or detection of the high-risk haplotype of in the majority (78%) of patients tested. These clinically actionable results guided medical care and improved patient outcomes.
慢性肾脏病(CKD)对儿童和成人都有较高的发病率和死亡率。在成人中,CKD通常与糖尿病并发症相关,而在这两类人群中,基因变异都可能是其潜在病因。从2016年更经济实惠的新一代测序(NGS)技术出现开始,特拉华州Nemours儿童医院的分子诊断实验室开发了首个具有临床可操作性的儿科NGS肾脏检测板,包含46个基因,其中包括。载脂蛋白L1()相关肾病在一系列非糖尿病肾病中都有报道。它与定义为G1和G2的两个“风险等位基因”显著相关,通常在非洲裔个体中发现。2020年初,随着新冠病毒在全球传播,肾衰竭患者的报告开始出现。在感染新冠病毒的黑人患者中发现的一种塌陷性肾小球病与已知的G1和/或G2风险变异的易感性有关。我们在11个已知与儿童期肾病综合征相关的基因()中鉴定出基因变异,或者在大多数(78%)检测患者中检测到的高风险单倍型。这些具有临床可操作性的结果指导了医疗护理并改善了患者预后。