P.5.10 Clinical and ultrastructural changes in transportinopathy

Muscle histopathological, ultrastructural and genetic features of a large Italian-Spanish family with autosomal dominant LGMD, previously mapped to 7q32.1–32.2 (LGMD1F) were studied in 3 biopsies. We collected the clinical history in 19 of 60 patients; muscle biopsy histopathology was investigated in one pair of affected patients (mother 1 biopsy, her daughter 2 consecutive biopsies at 9 and 22 years). We observed that the age of onset varied from 2 to 35 years, and occurred either in upper or in the lower girdle; in 14 cases there was hypotrophy both in proximal upper and in lower extremities in calf muscles. The severity was not increased in successive generations. Unreported clinical findings were arachnodactyly, dysphagia and dysarthria. Moreover, we noticed a discrepancy between the clinical severity and muscle biopsy involvement: the daughter has a more severe clinical course, the first biopsy had only type 1 fiber atrophy while increased fiber atrophy was observed in the second biopsy. The mother has a compromised muscle histopathology (more muscle fiber variation, and autophagic changes by acid phosphatase stain). An abnormal sarcomeric assembly is the cause of progressive atrophy and myofiber loss. Electron microscopy revealed accumulation of myofibrillar bodies in muscle fibers. Accumulation of desmin and myotilin and p62-positive aggregates was observed. A defect in transportin-3 gene has been found to be the cause of this disease, which represents a new mechanism of dominant myopathy. Our morphological and ultrastructural data seems to suggest a phenotype similar to myofibrillar disease; however, autophagosomes were also present. It is possible that SR protein cannot migrate or be transported in- and out-of the nuclear membrane.