Bi Jingru, Guo Wenkai, Ji Pengcheng, Li Shuang, Wang Peng, Li Qinggang, Xie Yuansheng
School of Medicine, Nankai University, Tianjin, China.
Department of Nephrology, First Medical Center of Chinese PLA General Hospital, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Medical Devices and Integrated Traditional Chinese and Western Drug Development for Severe Kidney Diseases, Beijing Key Laboratory of Digital Intelligent TCM for the Preventionand Treatment of Pan-vascular Diseases, Key Disciplines of National Administration of Traditional Chinese Medicine (zyyzdxk-2023310), Beijing, China.
Clin Kidney J. 2025 Mar 4;18(4):sfaf064. doi: 10.1093/ckj/sfaf064. eCollection 2025 Apr.
Cystic kidney disease is common. Beyond autosomal dominant polycystic kidney disease (ADPKD), knowledge of other hereditary forms of cystic kidney disease remains limited. This study aimed to retrospectively analyse 702 patients with multiple renal cysts from the Chinese PLA General Hospital (September 2015-December 2023).
Patients suspected of having hereditary cystic kidney disease underwent next-generation sequencing (NGS) and subsequent bioinformatics analysis. Variations were assessed for pathogenicity in accordance with the American College of Medical Genetics and Genomics (ACMG) guidelines. Moreover, the ClinVar and Mastermind databases were used to identify novel mutation sites. Statistical analysis was performed using SPSS 25.0 software.
Of 702 patients, 96 (13.7%) lacked gene mutations associated with cystic kidney disease. In contrast, 606 patients (86.3%) were found to have gene mutations associated with renal cyst phenotypes, involving 23 unique mutated genes. Among these, mutations in 158 patients were categorized as variants of uncertain significance. The remaining 448 patients harboured mutations predicted by the ACMG guidelines to be pathogenic or likely pathogenic, enabling a diagnosis of hereditary cystic kidney disease. These mutations were linked to seven diseases and 10 genes. The most common was ADPKD [434 cases (96.9%)], followed by autosomal dominant tubulointerstitial kidney disease [ADTKD; six cases (1.3%)], autosomal recessive polycystic kidney disease [ARPKD; five cases (1.1%)] and tuberous sclerosis complex [two cases (0.4%)]. One case each was found for autosomal dominant polycystic liver disease, -related disease and -related disease. The mutated genes included and . Moreover, 63 novel pathogenic or likely pathogenic variants were identified.
In this study we identified 23 mutated genes linked to renal cyst phenotypes, 10 of which had pathogenic or likely pathogenic variants. These findings facilitated the diagnosis of seven hereditary cystic kidney diseases, including ADPKD, ADTKD, ARPKD and others. Furthermore, 63 novel pathogenic or likely pathogenic variants were identified.
囊性肾病很常见。除常染色体显性遗传性多囊肾病（ADPKD）外，对其他遗传性囊性肾病的了解仍然有限。本研究旨在回顾性分析中国人民解放军总医院702例患有多发性肾囊肿的患者（2015年9月至2023年12月）。
疑似患有遗传性囊性肾病的患者接受了二代测序（NGS）及后续生物信息学分析。根据美国医学遗传学与基因组学学会（ACMG）指南评估变异的致病性。此外，使用ClinVar和Mastermind数据库识别新的突变位点。使用SPSS 25.0软件进行统计分析。
702例患者中，96例（13.7%）未检测到与囊性肾病相关的基因突变。相比之下，606例患者（86.3%）被发现存在与肾囊肿表型相关的基因突变，涉及23个独特的突变基因。其中，158例患者的突变被归类为意义未明的变异。其余448例患者携带ACMG指南预测为致病或可能致病的突变，从而得以诊断为遗传性囊性肾病。这些突变与7种疾病和10个基因相关。最常见的是ADPKD[434例（96.9%）]，其次是常染色体显性遗传性肾小管间质性肾病[ADTKD；6例（1.3%）]、常染色体隐性遗传性多囊肾病[ARPKD；5例（1.1%）]和结节性硬化症[2例（0.4%）]。常染色体显性遗传性多囊肝病、相关疾病和相关疾病各有1例。突变基因包括和。此外，还鉴定出63个新的致病或可能致病的变异。
在本研究中，我们鉴定出23个与肾囊肿表型相关的突变基因，其中10个具有致病或可能致病的变异。这些发现有助于诊断7种遗传性囊性肾病，包括ADPKD、ADTKD、ARPKD等。此外，还鉴定出63个新的致病或可能致病的变异。
Zotero 插件
