RYR recessive myopathy is a rare disease manifesting with a wide spectrum of clinical and morphological phenotypes. Here we present the histological and ultrastructural analysis of muscle biopsy from 50 patients with genetically confirmed RYR1 recessive myopathy. Up to 30% presented classical core myopathy, 12% core and rods, 8% type1 uniformity, 2% congenital fiber type disproportion and almost 50% showed a characteristic variable combination of sarcomeric disorganization, protein accumulation, type1 predominance and nuclear internalization. In the latter group, in addition, some patients presented rods, or/and areas of disorganization with targetoid appearance. Ultrastructural study has been performed in 35 patients. Regardless of histological findings, by electron microscopy all but two patients presented various degree of disorganization ranging from z-line duplication or smearing to larger areas of myofibrillar disorganization including more than 50 sarcomeres and occupying almost the entire fiber diameter. Frequently, different kinds of these areas were detected in the same biopsy. Pure disorganization was observed in one third of patients, whereas 25% showed also small areas of sarcomeric disorganization containing short elements resembling minirods rising from z-line fragments, 20% contained also subsarcolemmal rods outside sarcomeric disorganization areas and in 10% rods where detected only in atrophic fibers. In conclusion RyR1 recessive myopathy seems to manifest as continuum spectrum of histological and ultrastructural alterations in which myofibrillar disorganization ranges from very mild to severe. Moreover, levels of RyR1 expression in muscle biopsies have been assessed by Western Blot in several patients and its pertinence with genetics background, clinical severity and morphological findings has been investigated.
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