Abstract
IntroductionMiyoshi myopathy, a type of distal myopathy with predominant involvement of the posterior calf muscles, has been assigned to mutations in the dysferlin gene. However, many of the late-onset limb-girdle and distal myopathies that resemble dysferlinopathy or Miyoshi myopathy remain unclassified, even after extensive immunohistological and genetic analysis.Case presentationWe report the case of a 59-year-old Caucasian man with distal myopathy and exercise-induced myalgia, preferentially of the leg muscles, closely resembling the Miyoshi phenotype. Magnetic resonance imaging of his calf muscles showed typical fatty replacement of the medial heads of the gastrocnemius muscles and soleus muscles, with progression to the adductor longus muscles over a time course of two years. However, genetic analysis revealed that the phenotype of our patient was not related to a mutation in the dysferlin gene but to a novel homozygous splice mutation in the anoctamin 5 gene. Mutations in the anoctamin 5 gene have so far been identified only in some cases of limb-girdle and distal myopathy. Mutations in the anoctamin 5 gene have been assigned to limb-girdle muscular dystrophy type 2L, while distal Miyoshi-like phenotypes have been classified as Miyoshi myopathy type 3.ConclusionThe case presented in this report further strengthens the underlying genetic heterogeneity in Miyoshi myopathy-like phenotypes and adds another family to non-dysferlin, Miyoshi myopathy type 3 of late-onset. Furthermore, our case supports the recent observation that anoctamin 5 mutations are a primary cause of distal non-dysferlin myopathies. Therefore, given the increasing number of anoctamin 5 mutations in Miyoshi-like phenotypes, genetic analysis should include an anoctamin 5 screen in late-onset limb-girdle and distal myopathies.
Highlights
Miyoshi myopathy, a type of distal myopathy with predominant involvement of the posterior calf muscles, has been assigned to mutations in the dysferlin gene
The case presented in this report further strengthens the underlying genetic heterogeneity in Miyoshi myopathy-like phenotypes and adds another family to non-dysferlin, Miyoshi myopathy type 3 of late-onset
Our case supports the recent observation that anoctamin 5 mutations are a primary cause of distal non-dysferlin myopathies
Summary
We present a case of a patient with late-onset, nondysferlin MM with an underlying, novel splice mutation in ANO5. The mutation described here is associated with reduced sarcolemmal dysferlin and granular cytoplasmic dysferlin accumulation on immunohistochemistry while dysferlin immunoblot shows equal protein levels to controls. It remains to be proven whether other types of anoctaminopathies show this pattern of dysferlin expression. Authors’ contributions CN participated in the examination of the patient, the design and coordination of the study and drafted the manuscript. CSG participated in the examination of the patient, the design and coordination and helped to draft and revise the manuscript for important intellectual content. Author details 1Department of Neurology, University of Ulm, Ulm 89081, Germany. 2Institute of Neuropathology, University Hospital Münster, Münster 48149, Germany. 3Institute of Human Genetics, University of Würzburg, Biozentrum, Am Hubland, Würzburg 97074, Germany. 4Department of Neurology, University of Bochum, St Josef Hospital, Bochum 44791, Germany
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