HNF1B型
包装D1
医学
队列
病因学
基因
基因检测
疾病
肾脏疾病
内科学
病理
遗传学
多囊肾病
生物
基因表达
同源盒
作者
Andrea Domingo-Gallego,Marc Pybus,Gemma Bullich,Mónica Furlano,Laia Ejarque-Vila,Laura Lorente-Grandoso,Patricia Ruíz,Gloria Fraga,María López González,Juan Alberto Piñero‐Fernández,Lidia Rodríguez-Peña,Isabel Llano-Rivas,Raquel Sáez,Anna Bujons-Tur,Gema Ariceta,Lluís Guirado,Roser Torra,Elisabet Ars
摘要
Inherited kidney diseases are one of the leading causes of chronic kidney disease (CKD) that manifests before the age of 30 years. Precise clinical diagnosis of early-onset CKD is complicated due to the high phenotypic overlap, but genetic testing is a powerful diagnostic tool. We aimed to develop a genetic testing strategy to maximize the diagnostic yield for patients presenting with early-onset CKD and to determine the prevalence of the main causative genes.We performed genetic testing of 460 patients with early-onset CKD of suspected monogenic cause using next-generation sequencing of a custom-designed kidney disease gene panel in addition to targeted screening for c.428dupC MUC1.We achieved a global diagnostic yield of 65% (300/460), which varied depending on the clinical diagnostic group: 77% in cystic kidney diseases, 76% in tubulopathies, 67% in autosomal dominant tubulointerstitial kidney disease, 61% in glomerulopathies and 38% in congenital anomalies of the kidney and urinary tract. Among the 300 genetically diagnosed patients, the clinical diagnosis was confirmed in 77%, a specific diagnosis within a clinical diagnostic group was identified in 15%, and 7% of cases were reclassified. Of the 64 causative genes identified in our cohort, 7 (COL4A3, COL4A4, COL4A5, HNF1B, PKD1, PKD2 and PKHD1) accounted for 66% (198/300) of the genetically diagnosed patients.Two-thirds of patients with early-onset CKD in this cohort had a genetic cause. Just seven genes were responsible for the majority of diagnoses. Establishing a genetic diagnosis is crucial to define the precise aetiology of CKD, which allows accurate genetic counselling and improved patient management.
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