Key result
Heterozygous single nucleotide deletions in the last exon of the ACTN2 gene cause a novel, slowly progressive dominant distal myopathy with facial weakness.
Case Report
Out-of-frame mutations in the last exon of the ACTN2 gene cause a novel form of dominant distal myopathy with facial weakness.
Suggests novel actininopathy with isolated distal and facial weakness; leaves open diagnostic implications in atypical myopathies.
Background and Objectives To clinically, genetically, and histopathologically characterize patients presenting with an unusual combination of distal myopathy and facial weakness, without involvement of upper limb or shoulder girdle muscles. Methods Two families with a novel form of actininopathy were identified. Patients had been followed up over 10 years. Their molecular genetic diagnosis was not clear after extensive investigations, including analysis of candidate genes and FSHD1-related D4Z4 repeats. Results Patients shared a similar clinical phenotype and a common pattern of muscle involvement. They presented with a very slowly progressive myopathy involving anterior lower leg and facial muscles. Muscle MRI finding showed complete fat replacement of anterolateral compartment muscles of the lower legs with variable involvement of soleus and gastrocnemius but sparing thigh muscles. Muscle biopsy showed internalized nuclei, myofibrillar disorganization, and rimmed vacuoles. High-throughput sequencing identified in each proband a heterozygous single nucleotide deletion (c.2558del and c.2567del) in the last exon of the ACTN2 gene. The deletions are predicted to lead to a novel but unstructured slightly extended C-terminal amino acid sequence. Discussion Our findings indicate an unusual form of actininopathy with specific molecular and clinical features. Actininopathy should be considered in the differential diagnosis of distal myopathy combined with facial weakness.
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Savarese et al. (2021) conducted a case report in Distal myopathy with facial weakness. Heterozygous single nucleotide deletions (c.2558del and c.2567del) in the last exon of the ACTN2 gene was evaluated on Clinical, genetic, and histopathological characterization. Heterozygous single nucleotide deletions in the last exon of the ACTN2 gene cause a novel, slowly progressive dominant distal myopathy with facial weakness.
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