A Novel LDB3 Mutation Identified in Patients with Late-Onset Myofibrillar Myopathy

Objective: Inherited myopathies are a diverse group of genetic muscle disorders characterized by muscle weakness and dysfunction resulting from mutations in genes with a wide range of biological functions. This study was performed to elucidate genetic causes in a large family with late-onset myofibrillar myopathy.Methods: Whole-exome sequencing was first applied to the proband, and then subsequent filtering process and in silico analysis was performed to determine causative mutation.Results: This study identified an unreported likely pathogenic mutation, p.Met160Ile, in the LIM domain binding 3 (LDB3) gene. This missense mutation showed complete cosegregation with affected individuals and was located at an evolutionarily well-conserved site. Several in silico analyses, along with simulations of three-dimensional structural changes in the mutant protein, predicted its potential pathogenicity.Conclusion: These findings expand the current understanding of the genetic basis of inherited myopathy and underscore the importance of comprehensive genetic analysis in clinical practice.