ORIGINAL RESEARCH article
Front. Genet.
Sec. Genetics of Common and Rare Diseases
LRRC56 Deficiency Cause Motile Ciliopathies in Humans and Mice
Provisionally accepted
- 1Second Xiangya Hospital, Central South University, Changsha, China
- 2Department of Cell Biology, School of Life Sciences, Central South University, Changsha, China
- 3The Second Department of Thoracic Surgery,Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University,, Changsha, China
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Motile ciliopathies represent a group of disorders caused by impaired motility of cilia and flagella, resulting in clinical manifestations such as laterality defects, asthenospermia, chronic respiratory infections, and hydrocephalus. Although nearly 53 genes have been implicated, the genetic etiology remains unresolved in approximately 30% of cases, and the regulatory mechanisms of motile ciliogenesis are still incompletely understood. In this study, we identified a novel homozygous frameshift variant in LRRC56 (c.148delG, p. Val50Trpfs*22) in a patient presenting with laterality defects and recurrent pulmonary infections. High-speed video microscopy of nasal cilia from the proband demonstrated severely dyskinetic motion, despite the absence of obvious ultrastructural defects on conventional transmission electron microscopy. To explore the pathophysiological mechanism, we generated Lrrc56 knockout mice, which recapitulated the patient's laterality defects and also exhibited additional phenotypes consistent with motile ciliopathies, including male infertility, hydrocephalus, and defective mucociliary clearance. Quantitative proteomic analysis revealed markedly reduced expression of cilia-associated proteins, particularly microtubule inner proteins (MIPs) and axonemal dynein assembly factors, in Lrrc56-deficient tissues compared with wild-type controls. Our findings establish LRRC56 as an essential regulator of ciliary motility and highlight its role in the pathogenesis of motile ciliopathies.
Keywords: LRRC56, Mice, Motile cilia, Mutation, primary ciliary dyskinesia
Received: 02 Jul 2025; Accepted: 03 Nov 2025.
Copyright: © 2025 Xie, Gu, Yang, Yuan, Qin and Tan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Zhi-Ping Tan, zhipingtan@csu.edu.cn
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