title: Massive muscle cell degeneration in the early stage of merosin-deficient congenital muscular dystrophy.
abstract: Primary merosin-deficient congenital muscular dystrophy (CMD) is a severe form of congenital muscular disorder which is caused by mutations in the laminin alpha2 chain gene (LAMA2). The disease is characterized by marked dystrophic changes in skeletal muscles during early infancy, while little is known about the pathological process of the muscle fiber degeneration. Here, we report the immunohistochemical analysis of skeletal muscle in ten patients with primary merosin-deficient CMD using a panel of molecular markers for skeletal muscle proteins, cellular necrosis, and apoptosis. In the youngest patient (a 52 day old baby), prominent massive muscle cell degeneration occurred in association with the deposition of the C5-9 complement membrane attack complex (MAC). Most of the MAC-positive muscle fibers showed a severely deranged immunoreaction to dystrophin, dystroglycans, and other sarcolemmal proteins. In addition, we found scattered positive signals for apoptosis. Similar but milder changes were also observed in six other patients younger than 1 year. In the patients older than 3 years, muscle fibers positive for MAC and apoptotic signals were barely detectable. These findings imply that massive muscle fiber degeneration occurs in the very early stage of merosin-deficient CMD and may contribute to the severe dystrophic changes in muscle from early infancy.
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, NCNP, Ogawa-Higashi, Kodaira, Tokyo, Japan.
authors.forename: Y K
authors.initials: YK
authors.lastname: Hayashi
authors.forename: Z
authors.initials: Z
authors.lastname: Tezak
authors.forename: T
authors.initials: T
authors.lastname: Momoi
authors.forename: I
authors.initials: I
authors.lastname: Nonaka
authors.forename: C A
authors.initials: CA
authors.lastname: Garcia
authors.forename: E P
authors.initials: EP
authors.lastname: Hoffman
authors.forename: K
authors.initials: K
authors.lastname: Arahata
mesh_terms: D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007797:Laminin / Q000172:deficiency*; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology*; D009136:Muscular Dystrophies / Q000151:congenital* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism / Q000473:pathology
chemical_list: D007797:Laminin