Atrophy, fibrosis, and increased PAX7-positive cells in pharyngeal muscles of oculopharyngeal muscular dystrophy patients.

Abstract

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominant inherited dystrophy caused by an abnormal trinucleotide repeat expansion in the poly(A)-binding-protein-nuclear 1 (PABPN1) gene. Primary muscular targets of OPMD are the eyelid elevator and pharyngeal muscles, including the cricopharyngeal muscle (CPM), the progressive involution of which leads to ptosis and dysphagia, respectively. To understand the consequences of PABPN1 polyalanine expansion in OPMD, we studied muscle biopsies from 14 OPMD patients, 3 inclusion body myositis patients, and 9 healthy controls. In OPMD patient CPM (n = 6), there were typical dystrophic features with extensive endomysial fibrosis and marked atrophy of myosin heavy-chain IIa fibers. There were more PAX7-positive cells in all CPM versus other muscles (n = 5, control; n = 3, inclusion body myositis), and they were more numerous in OPMD CPM versus control normal CPM without any sign of muscle regeneration. Intranuclear inclusions were present in all OPMD muscles but unaffected OPMD patient muscles (i.e. sternocleidomastoid, quadriceps, or deltoid; n = 14) did not show evidence of fibrosis, atrophy, or increased PAX7-positive cell numbers. These results suggest that the specific involvement of CPM in OPMD might be caused by failure of the regenerative response with dysfunction of PAX7-positive cells and exacerbated fibrosis that does not correlate with the presence of PABPN1 inclusions.

• Authors: Teresa Gidaro, Elisa Negroni, Sophie Perié, Massimiliano Mirabella, Jeanne Lainé, Jean Lacau St Guily, Gillian Butler-Browne, Vincent Mouly, Capucine Trollet
• Journal: Journal of neuropathology and experimental neurology (J Neuropathol Exp Neurol) Vol. 72 Issue 3 Pg. 234-43 (Mar 2013) ISSN: 1554-6578 [Electronic] England
• PMID: 23399899 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• PAX7 Transcription Factor
• PAX7 protein, human

Topics

• Adult
• Aged
• Aged, 80 and over
• Atrophy (pathology)
• Female
• Fibrosis (pathology)
• Fluorescent Antibody Technique
• Humans
• Male
• Middle Aged
• Muscular Dystrophy, Oculopharyngeal (metabolism, pathology)
• PAX7 Transcription Factor (biosynthesis)
• Pharyngeal Muscles (metabolism, pathology)