Identifying gene mutations of Chinese patients with polycystic kidney disease through targeted next‐generation sequencing technology

Abstract

Background Polycystic kidney disease (PKD) is the most common hereditary kidney disease. The main mutational genes causing autosomal dominant polycystic kidney disease (ADPKD) are PKD1 and PKD2 as well as some rare pathogenic genes. Unilateral PKD is rare in clinics, and its association with gene mutations is unclear. Methods Targeted next‐generation sequencing (NGS) was performed to detect the renal ciliopathy‐associated genes (targeted NGS panel including 63 genes) in PKD patients. Results Forty‐eight PKD1 and PKD2 mutation sites were detected in 44 bilateral PKD patients, of which 48 were PKD1 mutation sites (87.5%) and six were PKD2 mutation sites (12.5%). All of which exhibited typical ADPKD. Furthermore, we detected HNF1B heterozygous mutations in three families. Although these three patients showed HNF1B heterozygous mutations, their clinical characteristics differed and showed phenotypic heterogeneity. Conclusions Targeted NGS panel was helpful in detecting typical ADPKD patients and even in non‐typical PKD patients. Macromutation in HNF1B may lead to bilateral PKD. The 16 novel PKD gene mutation sites and two novel PKD2 gene mutation sites discovered in this study have some significance in genetic counseling for ADPKD patients, and increase the number of studied families and expand the mutation database of ADPKD.

Clinical application of a phenotype‐based NGS panel for differential diagnosis of inherited kidney disease and beyond

“…Sen et al reported the results of analysis of an SRNS‐targeted diagnostic gene panel performed for 302 patients, confirming genetic diagnoses in 26.6% of the patients 23 . Another study of 44 patients with typical PKD who underwent targeted NGS testing with 63 related genes revealed 48 related mutation sites in PKD1 and PKD2 24 …”