Harsányiová J1, Kráľová Trančíková A1, Turčanová Koprušáková M2, Kolísek M1

1Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Slovakia

2Clinic of Neurology, University Hospital in Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Slovakia

 

Miyoshi muscular dystrophy (MMD) is an autosomal recessive rare muscle wasting disease caused by mutations in gene encoding for dysferlin (DYSF).  MMD is characterized by early adulthood onset with dominant symmetrical muscle atrophy in distal lower limb muscles (especially m. gastrocnemius and m. soleus) with progression to proximal lower limb, thigh, and hip muscles. It could be assumed, that similar to other better researched muscle ailments, also patients with MMD have deteriorated Mg homeostasis. This assumption, however, remains to be answered by further research. 

Here we have examined by multiphoton confocal microscopy biopsies from m. soleus of compose heterozygote suffering from MMD and of his father (DYSF c.4076T>C) and brother (newly described DYSF mutation inherited from the mother, c.2864+1dupG) who are heterozygotes, but each carrying different mutation in DYSF.  

We focused on the detection of dysferlin in transversal and longitudinal cuts of m. soleus. Immuno-fluorescent staining of dysferlin and β-actin revealed differences in arrangement and appearance of the muscle fibres and bundles between MMD and heterozygote samples and absence of dysferlin protein in sarcolemma in MMD biopsies.  

Thus, new mutation DYSF c.2864+1dupG together with already known mutation DYSF c.4076T>C leads to MMD onset caused by the depletion of dysferlin from the sarcolemma of the myocytes.