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Novel Desmin Mutation Causing Myofibrillar Myopathy in a Hmong Family
Stefan Nicolau1, Benjamin M Howe2, Elie Naddaf1
1Department of Neurology, Mayo Clinic, Rochester, MN, United States.
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.
Insights
A novel desmin gene variant causes autosomal dominant myofibrillar myopathy (MFM) in a Hmong family, leading to progressive muscle weakness. Muscle biopsy and MRI findings aided genetic interpretation.
Area of Science:
- Neurology
- Genetics
- Muscle Diseases
Background:
- Myofibrillar myopathies (MFM) are inherited muscle disorders characterized by Z-disc protein aggregation.
- Desmin gene mutations are responsible for approximately 7% of MFM cases.
Observation:
- A Hmong family presented with autosomal dominant MFM, featuring distal muscle weakness starting in the fifth decade.
- The proband exhibited progressive weakness, while a sibling had elevated creatine kinase levels without symptoms.
Findings:
- Genetic testing identified a novel desmin p.Ser13Tyr variant, predicted to impact protein function.
- Muscle biopsy confirmed MFM, and MRI revealed specific muscle group involvement, including tensor fasciae latae and gastrocnemius.
Implications:
- This study identifies a new desmin variant associated with MFM, expanding the genetic landscape of the disease.
- Integrated analysis of clinical, histological, MRI, and genetic data is crucial for diagnosing desmin-related MFM.
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