Plectin Defects in Epidermolysis Bullosa Simplex With Muscular Dystrophy

Muscle Nerve. 2007 Jan;35(1):24-35. doi: 10.1002/mus.20655.

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

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Membrane / metabolism
  • Cell Membrane / pathology
  • Cell Membrane / ultrastructure
  • Child
  • Cytoplasm / metabolism
  • Cytoplasm / pathology
  • Cytoplasm / ultrastructure
  • Cytoskeleton / metabolism
  • Cytoskeleton / pathology
  • Cytoskeleton / ultrastructure
  • DNA Mutational Analysis
  • Desmosomes / metabolism
  • Desmosomes / pathology
  • Desmosomes / ultrastructure
  • Epidermolysis Bullosa Simplex / complications
  • Epidermolysis Bullosa Simplex / metabolism*
  • Epidermolysis Bullosa Simplex / pathology
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Immunohistochemistry
  • Male
  • Microscopy, Immunoelectron
  • Middle Aged
  • Muscle Fibers, Fast-Twitch / metabolism
  • Muscle Fibers, Fast-Twitch / pathology
  • Muscle Fibers, Fast-Twitch / ultrastructure
  • Muscle Fibers, Slow-Twitch / metabolism
  • Muscle Fibers, Slow-Twitch / pathology
  • Muscle Fibers, Slow-Twitch / ultrastructure
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / ultrastructure
  • Muscular Dystrophies / complications
  • Muscular Dystrophies / metabolism*
  • Muscular Dystrophies / pathology
  • Mutation / genetics
  • Plectin / analysis
  • Plectin / genetics*
  • Plectin / metabolism*
  • Protein Structure, Tertiary / genetics

Substances

  • Plectin