■由拷贝数变异(CNVs)引起的基因组紊乱在肾病患者中很普遍;然而,他们对病因不明(uKF)的慢性肾衰竭(KF)的贡献尚不清楚。我们筛选了50岁或以下的uKF患者,以确定致病性CNV的患病率。
■我们招募了KF发病年龄≤50年的患者,以初步审查病历,排除明确临床或组织病理学肾脏诊断的患者或已经确定的遗传性肾脏疾病患者。接下来,我们进行了基于单核苷酸多态性(SNP)阵列的CNV筛查.对所有检测到的CNV进行系统分类,并评估患者肾脏疾病的可能原因。另外使用全基因组测序在540个基因中筛选具有不能解释肾脏表型的CNV的患者的因果变异。
■我们招募了172名患者,其中123人接受了SNP阵列。在12名患者(9.8%)中鉴定出对应于已知基因组疾病的致病性CNV。确定的基因组疾病为三名患者提供了致病性肾脏诊断,所有这些人在18岁时都达到了KF。其余9例患者的CNV与肾脏疾病因果关系不明确。随后,全基因组测序在另外四名患者中提供了致病基因诊断,包括与检测到的CNV无关的两个诊断序列变体。
■基因组疾病在uKF队列中很普遍,在123例患者中,有5例被鉴定为致病性CNV。需要结合CNV和序列变体分析的进一步研究来阐明基因组疾病在肾脏疾病中的因果作用。
UNASSIGNED: Genomic disorders caused by copy number variations (CNVs) are prevalent in patients with kidney disease; however, their contribution to chronic kidney failure (KF) of undetermined aetiology (uKF) is unclear. We screened patients with uKF aged 50 years or younger to establish the prevalence of causative CNVs.
UNASSIGNED: We enrolled patients with an onset of KF ≤50 years from suspected undetermined aetiology for initial review of medical records to exclude patients with clear-cut clinical or histopathological kidney diagnoses or patients with already established genetic kidney diseases. Next, we performed single nucleotide polymorphism (SNP) array-based CNV screening. All the detected CNVs were systematically classified and evaluated as possible causes of the patient\'s kidney disease. Patients with CNVs not explaining the kidney phenotype were additionally screened for causal variants in 540 genes using whole-genome sequencing.
UNASSIGNED: We enrolled 172 patients, of whom 123 underwent SNP-array. Pathogenic CNVs corresponding to known genomic disorders were identified in 12 patients (9.8%). The identified genomic disorders provided a causative kidney diagnosis in three patients, all of whom had reached KF by age 18 years. The remaining nine patients had CNVs with unclear kidney disease causality. Subsequently, whole-genome sequencing provided a causative genetic diagnosis in an additional four patients, including two diagnostic sequence variants unrelated to the detected CNVs.
UNASSIGNED: Genomic disorders were prevalent in this cohort with uKF, and causative CNVs were identified in 5 of 123 patients. Further studies combining the analysis of CNVs and sequence variants are needed to clarify the causal role of genomic disorders in kidney disease.