Autosomal dominant polycystic kidney disease (ADPKD) is a well-described condition in which ~80% of cases have a genetic explanation, while the genetic basis of sporadic cystic kidney disease in adults remains unclear in ~30% of cases. This study aimed to identify novel genes associated with polycystic kidney disease (PKD) in patients with sporadic cystic kidney disease in which a clear genetic change was not identified in established genes. A next-generation sequencing panel analyzed known genes related to renal cysts in 118 sporadic cases, followed by whole-genome sequencing on 47 unrelated individuals without identified candidate variants. Three male patients were found to have rare missense variants in the X-linked gene Cilia And Flagella Associated Protein 47 (CFAP47). CFAP47 was expressed in primary cilia of human renal tubules, and knockout mice exhibited vacuolation of tubular cells and tubular dilation, providing evidence that CFAP47 is a causative gene involved in cyst formation. This discovery of CFAP47 as a newly identified gene associated with PKD, displaying X-linked inheritance, emphasizes the need for further cases to understand the role of CFAP47 in PKD.

The authors have declared no competing interest.

This research was supported by AMED under Grant Number 22ek0109554h0002; JSPS KAKENHI Grant Numbers 22K19518, 19H03672, 21K08249, 19K17733, 22K16233, 20K22926, 22H03085, 19H01049; NHGRI grants U01 HG011744 and U24 HG011746; National Natural Science Foundation of China (32100480, 32370654). DEM is supported by NIH grant DP5OD033357. This work was also supported by 389 crowdfunding backers on the READYFOR platform (https://readyfor.jp/projects/tmd-kid)): Number 91AA003949.

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This study was approved by the Institutional Review Board of Tokyo Medical and Dental University (approval numbers #G2000-081 and #M2019-324) and conducted in accordance with the Declaration of Helsinki. All participants provided written informed consent and agreed to the use of their DNA and kidney tissues in research aimed at identifying genetic risk variants for kidney function. Additionally, all participants consented to the publication of their genetic and medical data in academic journals, provided that the data were anonymized.

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