# ACTA1‐Related Adult‐Onset Scapuloperoneal Myopathy With Cores and Rods

## TL;DR

A new case of adult-onset muscle disease linked to a rare ACTA1 gene variant is described, showing a unique pattern of muscle weakness and structural changes.

## Contribution

A novel ACTA1 variant (Pro334Leu) is identified in a late-onset scapuloperoneal myopathy with cores and rods, expanding the known clinical spectrum of actinopathies.

## Key findings

- The patient had a slowly progressive muscle weakness pattern affecting proximal and distal limb muscles.
- Muscle biopsy revealed cores and rods, and increased cardiac alpha-actin expression was observed.
- The Pro334Leu ACTA1 variant is a previously unpublished pathogenic mutation associated with a milder actinopathy phenotype.

## Abstract

Actinopathies are myopathies associated with pathogenic variants in ACTA1, a gene encoding the skeletal alpha‐actin protein. Although patients most frequently have a severe congenital myopathy, an important clinical and myopathological variability has been described. Recently, a scapuloperoneal myopathy phenotype associated with ACTA1 has been reported. Here, we present a Russian woman with a late‐onset, slowly progressive, scapuloperoneal actinopathy associated with an unpublished heterozygous pathogenic ACTA1 variant.

We performed a thorough analysis of clinical, muscle imaging, muscle biopsy, genetic, protein and cardiac alpha‐actin expression data from a 65‐year‐old woman with a scapuloperoneal myopathy phenotype.

Disease onset was at around 30 years with proximal lower limbs muscle weakness, which slowly progressed towards an upper and lower limb distal involvement with prominent weakness of the fourth and fifth finger extensors. A muscle MRI showed a symmetric axial involvement, while lower limbs sections evidenced a severe symmetric involvement of quadriceps and biceps femoris long head, and a symmetric involvement of medial gastrocnemius associated with a right tibialis anterior involvement. Muscle biopsy showed cores and rods. The patient harboured the unpublished NM_001100.4:c.1001C > T, p.(Pro334Leu) ACTA1 variant. Immunofluorescence and western blot studies showed an increased expression of cardiac alpha‐actin, an actin isoform which is normally predominant in the prenatal skeletal muscles and adult heart muscle, suggesting a possible role of this isoform in milder actinopathy phenotypes.

We report a milder, late‐onset, slowly progressive scapuloperoneal myopathy phenotype with cores and rods and cardiac alpha‐actin overexpression, thus expanding the spectrum of actinopathies.

Actinopathies are clinically, genetically, and myopathologically heterogeneous myopathies associated with pathogenic variants in ACTA1, a gene encoding skeletal alpha‐actin.A scapuloperoneal phenotype related to ACTA1 has been previously described in one family.We report a patient with an adult‐onset, slowly progressive, scapuloperoneal myopathy with cores and rods, harbouring the ACTA1 NM_001100.4:c.1001C > T, p.(Pro334Leu) heterozygous variant.The scapuloperoneal phenotype could represent a distinct clinical subcategory, and the characterisation of this patient with a less severe, different clinical presentation and cores and rods contributes to its understanding.

Actinopathies are clinically, genetically, and myopathologically heterogeneous myopathies associated with pathogenic variants in ACTA1, a gene encoding skeletal alpha‐actin.

A scapuloperoneal phenotype related to ACTA1 has been previously described in one family.

We report a patient with an adult‐onset, slowly progressive, scapuloperoneal myopathy with cores and rods, harbouring the ACTA1 NM_001100.4:c.1001C > T, p.(Pro334Leu) heterozygous variant.

The scapuloperoneal phenotype could represent a distinct clinical subcategory, and the characterisation of this patient with a less severe, different clinical presentation and cores and rods contributes to its understanding.

We report a patient with an adult‐onset, slowly progressive, ACTA1‐related scapuloperoneal myopathy with cores and rods, determined by the heterozygous variant NM_001100.4:c.1001C > T, p.(Pro334Leu). The scapuloperoneal phenotype could represent a distinct subcategory, and the characterisation of this patient with a less severe, different clinical presentation and nemaline bodies should contribute to its understanding.