{
  "abstract": "Background Variants in the FHL1 gene are associated with a spectrum of rare X-linked hereditary myopathies. This study describes the clinical presentation and genetic basis of a novel FHL1 variant identified in a Chinese family with an inherited myopathy, aiming to delineate its phenotypic and genotypic characteristics.Methods Clinical data were collected from two symptomatic family members. The proband underwent a muscle biopsy. Genetic analysis was performed using whole-exome sequencing and Sanger sequencing of peripheral blood DNA. Bioinformatic tools were employed to predict the pathogenicity of the variant and its impact on protein structure and stability. Wild-type and mutant FHL1 constructs were transfected into 293 T cells to compare mRNA and protein expression levels via quantitative PCR and Western blot.Results Affected family members exhibited progressive lower limb weakness and muscle atrophy. Muscle biopsy revealed mild myopathic changes without reducing bodies. A heterozygous FHL1 c.505T>C (p.C169R) variant was identified in the proband and other affected family members, while her nephew carried a hemizygous variant. Bioinformatics analysis predicted the variant to be damaging, and structural analysis indicated altered secondary structure and reduced protein stability. While mRNA levels remained unchanged in transfected 293 T cells, mutant FHL1 protein expression was significantly reduced in this heterologous system.Conclusion The FHL1 c.505T>C (p.C169R) variant is likely pathogenic and associated with a familial myopathy. The reduction in mutant protein expression may contribute to the disease mechanism. This finding expands the spectrum of FHL1-related myopathy reported in the Chinese population and underscores the importance of integrated genetic and clinical analyses for diagnosis.",
  "authors": [
    {
      "affiliations": [
        "Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China"
      ],
      "name": "Shuyi Zhang"
    },
    {
      "affiliations": [
        "Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China"
      ],
      "name": "Xiaoli Cao"
    },
    {
      "affiliations": [
        "Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China"
      ],
      "name": "Xianghong Wu"
    },
    {
      "affiliations": [
        "Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China"
      ],
      "name": "Wen Huang"
    }
  ],
  "title": "Clinical and genetic analysis of a family with myopathy caused by an FHL1 gene variant",
  "uid": "3dec86bb-6722-5890-b093-6c8b7e568bd6"
}