Rod distribution and muscle fiber type modification in the progression of nemaline myopathy

Abstract

Nemaline myopathy is a structural congenital myopathy associated with the presence of rodlike structures inside the muscle fibers and type I predominance. It may be caused by mutations in at least five genes: slow a-tropomyosin 3 (chromosome 1q22-23), nebulin (chromosome 2q21.1-q22), actin (chromosome 1q42), tropomyosin 2 (chromosome 9p13), and troponin T1 (chromosome 19q13.4). The effect of these mutations in the expression of the protein and the mechanism of rod formation is still under investigation. We analyzed the possibility of progressive alterations with time and/or disease evolution, such as transformation of type I to type II fiber and rod pattern and distribution in muscle fibers from patients with nemaline myopathy, through a morphometric and immunohistochemical analysis of different muscle protein isoforms. A tendency of diffuse rods to be organized in the subsarcoleminal region was observed in two patients who were submitted to subsequent biopsies after 10 and 13 years. Additionally, we observed the expression of type II protein isoforms in type I fibers and a higher proportion of type II fibers in the younger patient of a pair of affected sibs, giving further support to the hypothesis of progressive conversion of type II to type I fibers in nemaline myopathy.Univ Sao Paulo, Ctr Estudos Genoma Humano, IB, Dept Biol,Sch Med, BR-05508900 Sao Paulo, BrazilUniv Sao Paulo, Ctr Estudos Genoma Humano, IB, Dept Neurol,Sch Med, BR-05508900 Sao Paulo, BrazilUNIFESP, EPM, Dept Neurol, Sao Paulo, BrazilUniv Fed Parana, Div Neurol, Dept Internal Med, Hosp Clin, BR-80060000 Curitiba, Parana, BrazilHarvard Univ, Sch Med, Div Genet, Childrens Hosp, Boston, MA USAUNIFESP, EPM, Dept Neurol, Sao Paulo, BrazilWeb of Scienc