CFAP47 is Implicated in X-Linked Polycystic Kidney Disease

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports Pub Date : 2024-12-01 DOI:10.1016/j.ekir.2024.09.013

Takayasu Mori , Takuya Fujimaru , Chunyu Liu , Karynne Patterson , Kouhei Yamamoto , Takefumi Suzuki , Motoko Chiga , Akinari Sekine , Yoshifumi Ubara , Danny E. Miller , Miranda P.G. Zalusky , Shintaro Mandai , Fumiaki Ando , Yutaro Mori , Hiroaki Kikuchi , Koichiro Susa

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Abstract

Introduction

Autosomal dominant polycystic kidney disease (ADPKD) is a well-described condition in which approximately 80% of all cases have a genetic explanation; and among sporadic cases without a family history, the genetic bases remain unclear in approximately 30% of cases. This study aimed to identify 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.

Methods

A next-generation sequencing panel analyzed known genes related to kidney cysts in 118 sporadic cases, followed by whole-genome sequencing (WGS) on 47 unrelated individuals without identified candidate variants. Immunohistology examination was then conducted on both human kidney tissue and kidneys from CFAP47^−/Y mice.

Results

Three male patients were found to have rare missense variants in the X-linked gene cilia and flagella-associated protein 47 (CFAP47), none of whom had a family history of the condition. CFAP47 was expressed in primary cilia of human kidney tubules, and knockout (KO) mice exhibited vacuolation of tubular cells and tubular dilation, providing evidence that CFAP47 is a causative gene involved in cyst formation.

Conclusion

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.

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CFAP47与x连锁多囊肾病有关

常染色体显性多囊肾病（ADPKD）是一种描述良好的疾病，大约80%的病例有遗传解释；在没有家族史的散发病例中，大约30%的病例的遗传基础仍不清楚。本研究旨在鉴定散发性囊性肾病患者中与多囊性肾病（PKD）相关的基因，其中在已建立的基因中未发现明确的遗传变化。方法：新一代测序小组分析了118例散发病例中与肾囊肿相关的已知基因，随后对47名未确定候选变异的非相关个体进行了全基因组测序（WGS）。然后对人肾组织和CFAP47-/Y小鼠肾脏进行免疫组织学检查。结果：3例男性患者发现纤毛和鞭毛相关蛋白47 (CFAP47) x连锁基因存在罕见的错义变异，且均无家族史。CFAP47在人肾小管原代纤毛中表达，敲除（KO）小鼠表现出小管细胞空泡化和小管扩张，证明CFAP47是参与囊肿形成的致病基因。结论：CFAP47是新发现的PKD相关基因，具有x连锁遗传，需要进一步研究CFAP47在PKD中的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Kidney International Reports Medicine-Nephrology

CiteScore

7.70

自引率

3.30%

发文量

1578

审稿时长

8 weeks

期刊介绍： Kidney International Reports, an official journal of the International Society of Nephrology, is a peer-reviewed, open access journal devoted to the publication of leading research and developments related to kidney disease. With the primary aim of contributing to improved care of patients with kidney disease, the journal will publish original clinical and select translational articles and educational content related to the pathogenesis, evaluation and management of acute and chronic kidney disease, end stage renal disease (including transplantation), acid-base, fluid and electrolyte disturbances and hypertension. Of particular interest are submissions related to clinical trials, epidemiology, systematic reviews (including meta-analyses) and outcomes research. The journal will also provide a platform for wider dissemination of national and regional guidelines as well as consensus meeting reports.