Myofiber degeneration in autosomal dominant Emery-Dreifuss muscular dystrophy (AD-EDMD) (LGMD1B).
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.
Mittelbronn
Michel
M
Institute of Brain Research, University of Tübingen, Tübingen, Germany.
Hanisch
Frank
F
Gleichmann
Marc
M
Stötter
Mechthild
M
Korinthenberg
Rudolf
R
Wehnert
Manfred
M
Bonne
Gisèle
G
Rudnik-Schöneborn
Sabine
S
Bornemann
Antje
A
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
C494847:LMNA protein, human; D034904:Lamin Type A; D003402:Creatine Kinase