Autosomal dominant distal myopathy due to p.Ser85Cys mutation in the MATR3 gene: Novel case series and literature review.

Background: Matrin-3 autosomal dominant myopathy, most commonly caused by a Ser85Cys (S85C) missense mutation, is a rare distal myopathy, presenting a heterogeneous phenotype.

Methods: We report the clinical, physiological, radiological, and histological features of the first Portuguese patients diagnosed with p.Ser85Cys MATR3-related myopathy using a specific gene panel dedicated to "distal myopathies". Additionally, a narrative review of the literature was performed to contextualize our findings within the broader landscape of MATR3-related pathologies.

Results: Our case series describes the clinical findings of three patients diagnosed and followed in our center. The first patient was a 57-year-old male presenting with lower limb weakness, followed by loss of muscle force for fine motor gestures in the distal upper limb. Neurological examination revealed important muscle atrophy of the distal limbs and symmetrical motor deficit. The second patient, the brother of the aforementioned subject, was a 54-year-old male with similar symptoms associated with dysphagia and dysphonia. The third patient was a 58-year-old female, unrelated to the previous patients, presenting with distal weakness in the upper limbs and severe Achillean contractures. All three patients were investigated using needle electromyography and whole-body magnetic resonance imaging that disclosed a fatty infiltration pattern in the gastrocnemius, soleus, and tibialis anterior muscles. A muscle biopsy was performed solely for one patient and revealed rimmed vacuoles, consistent with previous reports. Genetic analysis found the same mutation in all three cases: c.254C>G, p.Ser85Cys in the MATR3 gene. The literature review included nine articles reporting families diagnosed with the p.Ser85Cys mutation in the MATR3 gene, and the main phenotypes associated with this genetic variant.

Conclusions: Despite being a rare myopathy, with only a few cases reported, MATR3 gene mutations should be considered in patients with distal myopathy and rimmed vacuoles on muscle biopsy.