Novel Desmin Mutation Causing Myofibrillar Myopathy in a Hmong Family

Abstract

Myofibrillar myopathies (MFM) are a clinically and genetically heterogenous group of inherited myopathies characterized by aggregation of Z-disc proteins. Mutations in desmin account for ∼7% of MFM. We report here a Hmong family with an autosomal dominant MFM caused by a novel variant in the desmin gene. The proband presented with lower limb followed by upper limb weakness starting in the 5th decade. On examination, there was distal more than proximal muscle weakness. One sibling was similarly affected, while another had an asymptomatic elevation of creatine kinase. Genetic testing revealed a novel p.Ser13Tyr variant, which was predicted by in silico algorithms to alter protein function. Muscle biopsy revealed a MFM. Muscle MRI demonstrated selective involvement of the tensor fasciae latae, semitendinosus, sartorius, gracilis, gastrocnemius, soleus, and peroneus longus muscles. In this family, the histological and MRI findings assisted in the interpretation of genetic testing results.

Expanding Spectrum of Desmin-Related Myopathy, Long-term Follow-up, and Cardiac Transplantation

“…Three patients were described before. 14,15 Initial presentation was skeletal muscle involvement in 12 and cardiac disease in 13 patients. Over the span of the study, skeletal muscle involvement was present in 22 and cardiac involvement in 19 patients (Figure 2A).…”