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Myofiber degeneration in autosomal‐dominant Emery‐Dreifuss muscular dystrophy (AD‐EDMD) (LGMD1B)
Author(s) -
Bornemann Antje,
Mittelbronn Michel
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a398-c
Subject(s) - lmna , muscular dystrophy , lamin , myocyte , pathology , congenital muscular dystrophy , biology , anatomy , sarcolemma , extracellular matrix , skeletal muscle , microbiology and biotechnology , medicine , genetics , nucleus
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. 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 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.