G.P.288: Dysferlinopathy in Egypt: Clinical, Pathological and Genetic characteristics

Abstract

Dysferlinopathy is caused by mutations of the dysferlin gene (DYSF) on chromosome 2p13. This gave rise to a spectrum of neuromuscular disorders including: limb-girdle (LGMD2B) and distal muscular dystrophies (Miyoshi myopathy: MM). Aim: to study the clinical, pathological and genetic characteristics of dysferlinopathy patients in Egypt. Subjects & Methods: Patients were selected from those with progressive muscular dystrophy referred to Muscle and Nerve Research Laboratory, Cairo, Egypt. We studied 77 patients with dystrophic muscle biopsy. Patients had neurological assessment, family pedigree study, Serum Creatine Kinase, ECHO cardiography, electromyography and Dystrophin gene testing. A battery of histochemical tests, immunohistochemistry using both fluorescent and automated methods against a panel of antibodies were done. Mini-multiplex Western Blotting was also done. Genetic study of Dysferlin gene was done for some patients. We found 40 patients with limb-girdle muscular dystrophy, 12 with dysferlinopathy, 6 with calpainopathy, 6 with sarcoglycanopathy and 16 with non-specified limb-girdle muscular dystrophy. Dysferlinopathy patients showed 3 patients with proximal type, 3 patients with Miyoshi myopathy and 6 patients with anterior compartment myopathy. Weakness was asymmetrical in 5 patients and symmetrical in 7 patients. Some muscles were uniformly affected in most patients: gluteus maximus, hamstrings, gastrocnemius, tibialis anterior and deltoids. Pathological study showed dystrophic changes of all biopsies, mitochondrial changes in 2 biopsies and inflammatory changes in 3 biopsies. Dysferlin gene analysis was done for only 6 patients of 4 families, showed homozygous mutations in two families, one heterozygous mutation in one family, and no mutation (only polymorphisms) in one family. Dysferlinopathy is a common condition in Egypt. Many clinical, pathological and genetic characteristics are found and help in its diagnosis.