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[Preprint]. 2024 Apr 5:2024.04.05.24304760.
doi: 10.1101/2024.04.05.24304760.

CFAP47 is a novel causative gene implicated in X-linked polycystic kidney disease

Takayasu Mori  1 , Takuya Fujimaru  1 , Chunyu Liu  2   3 , Karynne Patterson  4 , Kohei Yamamoto  5 , Takefumi Suzuki  1 , Motoko Chiga  1 , Akinari Sekine  6   7 , Yoshifumi Ubara  6   7 , Danny E Miller  8   9 , Miranda Pg Zalusky  8 , Shintaro Mandai  1 , Fumiaki Ando  1 , Yutaro Mori  1 , Hiroaki Kikuchi  1 , Koichiro Susa  1 ; University of Washington Center for Rare Disease Research; Jessica X Chong  8   9 , Michael J Bamshad  8   9 , Yue-Qiu Tan  10   11 , Feng Zhang  2   3 , Shinichi Uchida  1 , Eisei Sohara  1
Affiliations

CFAP47 is a novel causative gene implicated in X-linked polycystic kidney disease

Takayasu Mori et al. medRxiv. .

Update in

  • CFAP47 is Implicated in X-Linked Polycystic Kidney Disease.
    Mori T, Fujimaru T, Liu C, Patterson K, Yamamoto K, Suzuki T, Chiga M, Sekine A, Ubara Y, Miller DE, Zalusky MPG, Mandai S, Ando F, Mori Y, Kikuchi H, Susa K; University of Washington Center for Rare Disease Research; Chong JX, Bamshad MJ, Tan YQ, Zhang F, Uchida S, Sohara E. Mori T, et al. Kidney Int Rep. 2024 Sep 24;9(12):3580-3591. doi: 10.1016/j.ekir.2024.09.013. eCollection 2024 Dec. Kidney Int Rep. 2024. PMID: 39698362 Free PMC article.

Abstract

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.

Keywords: CFAP47; X-linked; polycystic kidney disease; sporadic.

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Conflict of interest statement

Disclosure statement DEM is on a scientific advisory board at Oxford Nanopore Technologies (ONT), is engaged in a research agreement with ONT, and they have paid for his travel to speak on their behalf. DEM holds stock options in MyOme. The remaining authors have no relevant financial disclosures.

Figures

Figure 1.
Figure 1.. Summary of genetic analysis for a cohort of 118 cases with sporadic PKD.
Targeted NGS panel analysis covering cystic kidney disease-related genes was followed by targeted long-read sequencing (T-LRS) and whole-genome sequencing (WGS). This approach identified CFAP47 mutations in three cases, constituting 2.5% of the total cohort. #The proportion within the 49 unsolved cases.
Figure 2.
Figure 2.. Family tree and MRI of Polycystic Kidneys
Family trees, genetic mutations, and abdominal MRI images of K570 (Case 1), K698 (Case 2), and K1216 (Case 3) are shown in Panels A, B, and C, respectively.
Figure 3.
Figure 3.. Evaluation of CFAP47 expression sites in human kidney tubules and renal morphology of Cfap47−/Y mice
(A) Human kidney normal tubules co-immunostained with acetylated alpha-tubulin antibody (red) and CFAP47 antibody (green); arrowheads indicate positive staining sites; (B) Cfap47+/Y and Cfap47−/Y mouse kidney macro-morphology images; (C) Kidney Volume Comparison using the ellipsoid formula: (length × width × [π/6])2 (D) Low and high magnification images with Hematoxylin-Eosin Stain.
See this image and copyright information in PMC

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