Identification of eight genes associated with recurrent patellar dislocation

Zijie Xu; Siyuan Huang; Yifan Song; Chao Xu; Hongyu Yan; Ouyang Linkun; Bo Lv; Fuzhen Yuan; Bingbing Xu; Haijun Wang; Ruibin Xi; Jia-Kuo Yu

doi:10.1016/j.isci.2024.109697

Identification of eight genes associated with recurrent patellar dislocation

iScience. 2024 Apr 8;27(5):109697. doi: 10.1016/j.isci.2024.109697. eCollection 2024 May 17.

Authors

Zijie Xu^{1

2}, Siyuan Huang³, Yifan Song⁴, Chao Xu⁵, Hongyu Yan⁶, Ouyang Linkun³, Bo Lv⁷, Fuzhen Yuan^{1

2}, Bingbing Xu^{1

2}, Haijun Wang^{1

2}, Ruibin Xi⁸, Jia-Kuo Yu⁴

Affiliations

¹ Sports Medicine Department, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, China.
² Institute of Sports Medicine, Peking University, Beijing, China.
³ Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
⁴ Orthopaedic Sports Medicine Center, Beijing Tsinghua Changgung Hospital, Affiliated Hospital of Tsinghua University, Beijing, China.
⁵ The Department of Joint Surgery and Sports Medicine, The Second Affiliated Hospital of Xinjiang Medical University, Urumchi, China.
⁶ Department of Pediatric Neurology, Children's Hospital Affiliated to the Capital Institute of Pediatrics, Peking University, Beijing, China.
⁷ Department of Orthopedics, People's Hospital of Guilin, Guilin, Guangxi, China.
⁸ School of Mathematical Sciences and Center for Statistical Science, Peking University, Beijing, China.

Abstract

The inheritance of recurrent patellar dislocation (RPD) is known, but the susceptible gene remains unidentified. Here, we performed the first whole exome sequencing (WES) cohort study to identify the susceptible genes. The results showed eight genes were associated with this disease. Notably, the carboxypeptidase D (CPD) gene showed the highest relevance based on its gene function and tissue expression. Single-cell sequencing results indicate that the CPD gene is involved in the pathophysiological process of RPD through granulocytes. Implicated pathways include nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and Wnt/β-catenin signaling, potentially influencing CPD's role in RPD pathogenesis. This study identified the susceptible gene and investigates the potential pathogenesis of RPD, which provided a new prospect for the understanding of RPD. Besides, it would offer the theoretical basis for disease prevention and genetic counseling.

Keywords: Clinical genetics; Pathophysiology; Transcriptomics.