Abstract
Epidermolysis bullosa simplex with muscular dystrophy (EBS-MD, MIM 226670) is caused by plectin defects. We performed mutational analysis and immunohistochemistry using EBS-MD (n = 3 cases) and control skeletal muscle to determine pathogenesis. Mutational analysis revealed a novel homozygous plectin-exon32 rod domain mutation (R2465X). All plectin/HD1-121 antibodies stained the control skeletal muscle membrane. However, plectin antibodies stained the cytoplasm of type II control muscle fibers (as confirmed by ATPase staining), whereas HD1-121 stained the cytoplasm of type I fibers. EBS-MD samples lacked membrane (n = 3) but retained cytoplasmic HD1-121 (n = 1) and plectin staining in type II fibers (n = 3). Ultrastructurally, EBS-MD demonstrated widening and vacuolization adjacent to the membrane and disorganization of Z-lines (n = 2 of 3) compared to controls (n = 5). Control muscle immunogold labeling colocalized plectin and desmin to filamentous bridges between Z-lines and the membrane that were disrupted in EBS-MD muscle. We conclude that fiber-specific plectin expression is associated with the desmin-cytoskeleton, Z-lines, and crucially myocyte membrane linkage, analogous to hemidesmosomes in skin.
Publication types
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Case Reports
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Cell Membrane / metabolism
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Cell Membrane / pathology
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Cell Membrane / ultrastructure
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Child
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Cytoplasm / metabolism
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Cytoplasm / pathology
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Cytoplasm / ultrastructure
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Cytoskeleton / metabolism
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Cytoskeleton / pathology
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Cytoskeleton / ultrastructure
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DNA Mutational Analysis
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Desmosomes / metabolism
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Desmosomes / pathology
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Desmosomes / ultrastructure
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Epidermolysis Bullosa Simplex / complications
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Epidermolysis Bullosa Simplex / metabolism*
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Epidermolysis Bullosa Simplex / pathology
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Female
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Genetic Predisposition to Disease / genetics*
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Humans
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Immunohistochemistry
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Male
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Microscopy, Immunoelectron
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Middle Aged
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Muscle Fibers, Fast-Twitch / metabolism
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Muscle Fibers, Fast-Twitch / pathology
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Muscle Fibers, Fast-Twitch / ultrastructure
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Muscle Fibers, Slow-Twitch / metabolism
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Muscle Fibers, Slow-Twitch / pathology
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Muscle Fibers, Slow-Twitch / ultrastructure
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Muscle, Skeletal / metabolism*
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Muscle, Skeletal / pathology
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Muscle, Skeletal / ultrastructure
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Muscular Dystrophies / complications
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Muscular Dystrophies / metabolism*
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Muscular Dystrophies / pathology
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Mutation / genetics
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Plectin / analysis
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Plectin / genetics*
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Plectin / metabolism*
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Protein Structure, Tertiary / genetics