Harnan Sue, Gittus Matthew, Falzon Louise, Durkie Miranda, Mandrik Olena, Ong Albert C, Fotheringham James
Sheffield Centre for Health and Related Research, University of Sheffield, Sheffield, UK.
Sheffield Diagnostic Genetics Service, North East and Yorkshire Genomic Laboratory Hub, Sheffield Children's NHS Foundation Trust, Sheffield, UK.
Clin Kidney J. 2025 Jun 13;18(7):sfaf187. doi: 10.1093/ckj/sfaf187. eCollection 2025 Jul.
Genomic and ultrasound tests can provide diagnostic and prognostic information on autosomal-dominant polycystic kidney disease (ADPKD), and can screen first-degree relatives in whom early diagnosis can be advantageous. We conducted a systematic mapping review on test accuracy and characteristics over time.
Medline, Embase, and Cochrane were searched (August 2023) for studies in firstdegree relatives/individuals clinically diagnosed with ADPKD receiving genomic or ultrasound tests. Acceptable reference standards for sensitivity/detection rate and specificity were definitive imaging or genomic confirmation. Genomic studies were categorized by technology and read length. Relationships between sensitivity, specificity, genomic technology, diagnostic criteria/reference standard, and genes tested were compared.
From 1029 non-duplicate titles retrieved, 51 genomic and 7 ultrasound studies were included. There were no genomic studies in first-degree relatives. Among studies in patients with clinical diagnoses, genomic sequencing methodologies were highly heterogeneous [next generation (short read ( = 20), long read ( = 1)), targeted Sanger ( = 19), whole exome ( = 1) with additional multi-ligation probe analysis ( = 13)]. Median sensitivity was 78% (Interquartile range 65% to 88%). Ultrasound sensitivity and specificity generally improved with age and were worse in patients compared to (lowest reported 31% and 88%, respectively, in polycystic kidney disease () 2 patients aged 5-14; highest 100% and 100%, respectively, in multiple gene/age categories).
Despite technological advances, sensitivity of genomic tests appeared static between 2000 and 2023. Possible explanations include clinical diagnostic criteria (and hence populations recruited) widening from to include and atypical phenotypes, and small incremental gains of testing genes other than PKD1 and PKD2. For people at risk of ADPKD in genetically unresolved families, the accuracy of ultrasound is uncertain. Unified genomic test taxonomies would facilitate future reviews. PROSPERO CRD42023456727.
基因组检测和超声检测可为常染色体显性多囊肾病（ADPKD）提供诊断和预后信息，并可对一级亲属进行筛查，早期诊断可能有益。我们对检测准确性和特征随时间的变化进行了系统的图谱综述。
检索了Medline、Embase和Cochrane数据库（2023年8月），以查找接受基因组检测或超声检测的临床诊断为ADPKD的一级亲属/个体的研究。灵敏度/检测率和特异性的可接受参考标准为确定性成像或基因组确认。基因组研究按技术和读取长度分类。比较了灵敏度、特异性、基因组技术、诊断标准/参考标准和检测基因之间的关系。
从检索到的1029个非重复标题中，纳入了51项基因组研究和7项超声研究。没有针对一级亲属的基因组研究。在临床诊断患者的研究中，基因组测序方法高度异质[下一代（短读长（n = 20），长读长（n = 1）），靶向桑格测序（n = 19），全外显子组测序（n = 1）以及额外的多重连接探针分析（n = 13）]。中位灵敏度为78%（四分位间距65%至88%）。超声的灵敏度和特异性一般随年龄增长而提高，与成人相比，儿童患者的情况更差（在5至14岁的多囊肾病（PKD）2患者中，最低报告分别为31%和88%；在多个基因/年龄类别中，最高分别为100%和100%）。
尽管技术有所进步，但2000年至2023年间基因组检测的灵敏度似乎没有变化。可能的解释包括临床诊断标准（以及因此招募的人群）从PKD1扩大到包括PKD2和非典型表型，以及检测PKD1和PKD2以外的基因的增量收益较小。对于基因未明确的家庭中患ADPKD风险的人群，超声的准确性尚不确定。统一的基因组检测分类法将有助于未来的综述。PROSPERO注册号：CRD42023456727。
