Molecular Genetic Diagnosis of a Bethlem Myopathy Family with an Autosomal-Dominant COL6A1 Mutation, as Evidenced by Exome Sequencing
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Background We describe herein the application of whole exome sequencing (WES) for themolecular genetic diagnosis of a large Korean family with dominantly inherited myopathy. Case Report Te afected individuals presented with slowly progressive proximal weakness and ankle contracture. Tey were initially diagnosed with limb-girdle muscular dystrophy (LGMD) based on clinical and pathologic features. However, WES and subsequent capillary sequencing identifed a pathogenic splicing-site mutation (c.1056+1G>A) in COL6A1,which was previously reported to be an underlying cause of Bethlem myopathy. Afer identifcation of the genetic cause of the disease, careful neurologic examination revealed subtlecontracture of the interphalangeal joint in the afected members, which is a characteristicsign of Bethlem myopathy. Terefore, we revised the original diagnosis from LGMD to Bethlem myopathy. Conclusions Tis is the frst report of identifcation of COL6A1-mediated Bethlem myopathyin Korea, and indicates the utility of WES for the diagnosis of muscular dystrophy.
Abstract
Background We describe herein the application of whole exome sequencing (WES) for themolecular genetic diagnosis of a large Korean family with dominantly inherited myopathy. Case Report Te afected individuals presented with slowly progressive proximal weakness and ankle contracture. Tey were initially diagnosed with limb-girdle muscular dystrophy (LGMD) based on clinical and pathologic features. However, WES and subsequent capillary sequencing identifed a pathogenic splicing-site mutation (c.1056+1G>A) in COL6A1,which was previously reported to be an underlying cause of Bethlem myopathy. Afer identifcation of the genetic cause of the disease, careful neurologic examination revealed subtlecontracture of the interphalangeal joint in the afected members, which is a characteristicsign of Bethlem myopathy. Terefore, we revised the original diagnosis from LGMD to Bethlem myopathy. Conclusions Tis is the frst report of identifcation of COL6A1-mediated Bethlem myopathyin Korea, and indicates the utility of WES for the diagnosis of muscular dystrophy.
참고문헌 (17)
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