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ORIGINAL RESEARCH article

Front. Genet.
Sec. Genetics of Common and Rare Diseases
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1521412
This article is part of the Research Topic Insights in Genetics of Common and Rare Diseases 2024 View all 6 articles

Mutation in the COL2A1 gene is associated with acetabular dysplasia

Provisionally accepted
Miaomiao Xin Miaomiao Xin 1Xin Guan Xin Guan 1,2Jiangfei Yang Jiangfei Yang 3Yi Li Yi Li 4Zhentao Man Zhentao Man 4Hongsheng Sun Hongsheng Sun 1*Min Fu Min Fu 1*
  • 1 Department of Rheumatology and Immunology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, China
  • 2 Department of Rheumatology and Immunology, Xing'an League People's Hospital of Inner Mongolia, Ulan Hot, China
  • 3 Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, China
  • 4 Department of Joint Surgery and Sports Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, China

The final, formatted version of the article will be published soon.

    Background: Developmental dysplasia of the hip (DDH) is one of the most common developmental disorders worldwide, caused by a combination of genetic and environmental factors.Methods: To investigate the genetic etiology of DDH in a proband (a 27-year-old male), we reviewed the patient's clinical data and collected peripheral blood samples from the proband and his parents. Genomic DNA was extracted, and polymerase chain reaction (PCR) amplification was performed. Clinical whole-exome sequencing (WES) using next-generation sequencing (NGS) was conducted to identify potential mutation sites, which were then validated through Sanger sequencing. Bioinformatics analysis was performed to assess the pathogenicity of the identified variant, and 3D protein modeling was conducted to predict its impact on protein structure.Results: The proband presented with pain in bilateral hips, and based on clinical symptoms, laboratory findings and imaging studies, the final diagnosis was considered to be acetabular dysplasia with overlapping secondary synovial chondromatosis. Family history revealed similar symptoms in the proband's father, while the grandparents and other family members were unaffected. The patient underwent bilateral total hip arthroplasty and synovectomy. NGS and Sanger sequencing identified a heterozygous missense mutation in the COL2A1 gene (ex13, c.823C>T; p.Arg275Cys) in both the proband and his father, while this mutation was absent in the mother. Bioinformatic analysis indicated that the c.823C>T (p.Arg275Cys) variant is pathogenic, and structural modeling demonstrated that the substitution of arginine with cysteine at residue 275 altered the protein structure.Conclusions: Our findings highlight the diagnostic utility of NGS in identifying precise genetic causes of DDH. The identification of the COL2A1 gene mutation in this present case represents a novel clinical phenotype, expanding the spectrum of disorders associated with COL2A1 mutations.

    Keywords: COL2A1, Mutation, Synovial chondromatosis, Developmental dysplasia of the hip, the hip joints

    Received: 01 Nov 2024; Accepted: 20 Dec 2024.

    Copyright: © 2024 Xin, Guan, Yang, Li, Man, Sun and Fu. 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:
    Hongsheng Sun, Department of Rheumatology and Immunology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, China
    Min Fu, Department of Rheumatology and Immunology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, China

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