P.9.4

Abstract

Nemaline myopathy is one of the most common forms of congenital myopathy characterized pathologically by presence of nemaline rods in muscle fibers. Clinical features are quite variable from severe infantile form to adult onset milder form. Genetic diagnosis is not easy because several causative genes have been identified including a very much big gene like NEB . To know the frequency and clinical and pathological characteristics of each causative genes of nemaline myopathy. We chose more than 200 patients who were pathologically diagnosed to have nemaline myopathy from muscle repository in the National Center of Neurology and Psychiatry, Japan. Mutation screening is on going using a combination of the target re-sequencing by next generation sequencer and the direct sequencing by Sanger method. Mutations in ACTA1 were identified in 15.4% of the patients examined in our cohort. Clinically, most of the patients carrying ACTA1 mutation were sporadic and showed severe infantile form, but a family with autosomal dominant mild myopathy was also found. We identified many variants in NEB , RYR1 , and other causative genes in more than one third of our cohorts, but only one variant was found in many of these patients. Presence of unidentified genes was suggested because no mutation in the known causative genes was found in a half of nemaline myopathy. Other disorders can also produce pathological findings consistent with nemaline myopathy.