Key result
A novel frameshift variant (c.2504delT) in ACTN2 was identified in a Chinese family, causing an adult-onset distal myopathy with multi-minicores and abnormal Z-line organization.
Why the study?
Diverse phenotypes and limited known mutations in ACTN2-related myopathy have made genotype-phenotype correlations challenging to understand.
Case Report (n=3)
The identification of a novel ACTN2 frameshift variant expands the phenotypic spectrum of ACTN2-related myopathies to include adult-onset distal myopathy with multi-minicores.
Answers are grounded in this paper and cite their sources.
May prompt ACTN2 inclusion in distal myopathy panels; leaves open broader causality and prevalence pending larger studies.
INTRODUCTION: Distal myopathies are a group of rare muscle disorders characterized by selective or predominant weakness in the feet and/or hands. In 2019, ACTN2 gene was firstly identified to be a cause of a new adult-onset distal muscular dystrophy calling actininopathy and another distinctly different myopathy, named multiple structured core disease (MsCD). Thus, the various phenotypes and limited mutations in ACTN2-related myopathy make the genotype-phenotype correlation hard to understand. AIMS: To investigate the clinical features and histological findings in a Chinese family with distal myopathy. Whole exome sequencing and several functional studies were performed to explore the pathogenesis of the disease. RESULTS: We firstly identified a novel frameshift variant (c.2504delT, p.Phe835Serfs*66) within ACTN2 in a family including three patients. The patients exhibited adult-onset distal myopathy with multi-minicores, which, interestingly, was more like a combination of MsCD and actininopathy. Moreover, functional analysis using muscle samples revealed that the variant significantly increased the expression level of α-actinin-2 and resulted in abnormal Z-line organization of muscle fiber. Vitro studies suggested aggregate formations might be involved in the pathogenesis of the disease. CONCLUSION: Our results expanded the phenotypes of ACTN2-related myopathy and provided helpful information to clarify the molecular mechanisms.
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Chen et al. (2021) conducted a case report in Distal myopathy (n=3). ACTN2 frameshift variant (c.2504delT, p.Phe835Serfs*66) was evaluated on Clinical features and histological findings. A novel frameshift variant (c.2504delT) in ACTN2 was identified in a Chinese family, causing an adult-onset distal myopathy with multi-minicores and abnormal Z-line organization.
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