title: Myofiber degeneration in autosomal dominant Emery-Dreifuss muscular dystrophy (AD-EDMD) (LGMD1B).
abstract: Autosomal dominant Emery-Dreifuss muscular dystrophy is caused by mutations in the LMNA gene that code for the nuclear membrane protein lamin A/C. We investigated skeletal muscle fibers from several muscles for cytoplasmic degenerative changes in three patients with genetically confirmed Emery-Dreifuss muscular dystrophy. Methods included quantitative light and electron microscopy and PCR-based mutational analysis.
  
  
  RESULTS
  The degenerative pathway was characterized by the gradual replacement of individual myofibers by connective tissue. Early stages of degeneration typically involved only a segment of the cross-sectional area of a myofiber. Intermediate stages consisted of myofiber shrinkage due to "shedding" of peripheral cytoplasmic portions into the endomysial space, and fragmentation of the myofibers by interposed collagen fibrils. Empty basement membrane sheaths surrounded by abundant deposits of extracellular matrix marked the end stage of the degenerative process. The nuclear number-to-cytoplasmic area in myofibers of one patient increased with increasing cross-sectional area, suggesting that satellite cell fusion with myofibers may have compensated for myofiber shrinkage. The pattern of degeneration described herein differs from muscular dystrophies with plasma membrane defects (dystrophinopathy, dysferlinopathy) and explains the frequently found absence of highly elevated serum creatine kinase levels in autosomal dominant Emery-Dreifuss muscular dystrophy.
authors.affiliation: Institute of Brain Research, University of Tübingen, Tübingen, Germany.
authors.forename: Michel
authors.initials: M
authors.lastname: Mittelbronn
authors.forename: Frank
authors.initials: F
authors.lastname: Hanisch
authors.forename: Marc
authors.initials: M
authors.lastname: Gleichmann
authors.forename: Mechthild
authors.initials: M
authors.lastname: Stötter
authors.forename: Rudolf
authors.initials: R
authors.lastname: Korinthenberg
authors.forename: Manfred
authors.initials: M
authors.lastname: Wehnert
authors.forename: Gisèle
authors.initials: G
authors.lastname: Bonne
authors.forename: Sabine
authors.initials: S
authors.lastname: Rudnik-Schöneborn
authors.forename: Antje
authors.initials: A
authors.lastname: Bornemann
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D003402:Creatine Kinase / Q000097:blood; D004252:DNA Mutational Analysis; D006801:Humans; D034904:Lamin Type A / Q000235:genetics; D008297:Male; D046529:Microscopy, Electron, Transmission; D018485:Muscle Fibers, Skeletal / Q000473:pathology*; D018482:Muscle, Skeletal / Q000473:pathology*; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D009154:Mutation
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A; D003402:Creatine Kinase