G.P.58: The first Asian family having vocal cord and pharyngeal weakness with distal myopathy due to a MATR3 mutation

Abstract

Vocal cord and pharyngeal weakness with distal myopathy (VCPDM) is a rare, chronic, non-inflammatory myopathy characterized by rimmed vacuoles and is identified in North American and Bulgarian families. Recently, a missense mutation in the gene encoding for Matrin-3 (MATR3) was reported as one of the causes of VCPDM. However, the pathophysiology underlying the myofiber degeneration remains an enigma. Here, we report the clinical, radiological, and electrophysiological features of the members of the first Asian family having VCPDM along with the missense mutation in the MATR3 gene: p.S85C (c.254C>G), which was exactly the same mutation as described in the previous families with VCPDM. Muscle histology was examined in two affected members of the family to identify the histopathological characteristics of VCPDM. Patients with VCPDM exhibited clinical features suggesting intrafamilial variation including neuropathic presentation. Skeletal muscle magnetic resonance imaging (MRI) revealed myodegeneration that spared the quadriceps. Electrophysiological studies showed various myogenic and neurogenic changes. Muscle biopsies demonstrated non-inflammatory myopathic changes, specifically rimmed vacuoles, and the presence of sarcoplasmic aggregates of proteins like p62, TDP-43, and ubiquitin. Our findings suggest involvement of protein degradation and nuclear dysfunction in VCPDM pathogenesis. The MATR3 mutation may produce a phenotype of myopathy with rimmed vacuoles and neuropathy.