Abstract
Distal myopathies are a group of clinically and genetically heterogeneous hereditary muscle disorders characterized by progressive muscular weakness starting in the distal parts of the limbs. The most common subtype of distal myopathy is GNE myopathy, a rare muscle disease with autosomal recessive inheritance. Limb-girdle muscular dystrophy 2G (LGMD2G) is a rare autosomal recessive subtype of LGMDs caused by TCAP variant. Patients with LGMD2G can present with distal myopathy and rimmed vacuoles on muscle pathology. Thus far, the most reported TCAP mutations related to LGMD2G were recessive frameshift or nonsense variants. Here, we described four Chinese patients from unrelated families with LGMD2G due to TCAP mutations. The clinical symptoms of our patients were similar to those previously reported in LGMD2G patients. Three different pathogenic TCAP variants were identified in these patients, including two frameshift variants and one intronic variant. Autophagolysosomes have been observed in one patient by electron microscopy. Our research expands the genetic spectrum of TCAP mutations in China, indicating c.165-166insG is likely the common pathogenic variant. We also provide evidences that autophagy may be involved in the pathophysiology of LGMD2G.