oculopharyngeal muscular dystrophy

Pathology

• intranuclear filamentous inclusions or aggregates are detected in the myocytes of patients; these inclusions contain PABPN1, ubiquitin, subunits of the proteasome & poly(A) RNA
• the association of the expanded polyalanine mutations together with the capability to oligomerize may induce these inclusions & cell death
• expanded polyalanine mutations may either result from unequal crossing over during germ cell homologous recombination or from DNA slippage
• the pathogenic mechanisms mediated by polyalanine expansion mutations may be either a general disruption of cellular RNA metabolism due to the trapping by the inclusions of PABPN1, mRNAs &/or nuclear proteins, resulting in the induction of cell death; or may change normal muscle cell differentiation

Genetics

• autosomal dominant & autosomal recessive forms
• defects in polyadenylate-binding protein 2 (PABPN1)
• locus near region of cardiac alpha & beta myosin heavy chain genes

Clinical manifestations

• late-onset slowly progressive myopathy characterized by
  • eyelid ptosis
  • dysphagia
  • cranial muscle weakness & proximal limb weakness (sometimes)

More general terms

• muscular dystrophy
• polyalanine expansion disorder

Database

• OMIM: https://mirror.omim.org/entry/164300
• OMIM: https://mirror.omim.org/entry/602279
• OMIM: https://mirror.omim.org/entry/257950