Atrophy, Fibrosis, and Increased PAX7-Positive Cells in Pharyngeal Muscles of Oculopharyngeal Muscular Dystrophy Patients

Massimiliano Mirabella, Teresa Gidaro, Elisa Negroni, Sophie Perié, Jeanne Lainé, Jean Lacau St Guily, Gillian Butler-Browne, Vincent Mouly, Capucine Trollet

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

31 Citazioni (Scopus)

Abstract

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.
Lingua originaleEnglish
pagine (da-a)234-243
Numero di pagine10
RivistaJournal of Neuropathology and Experimental Neurology
Volume72
DOI
Stato di pubblicazionePubblicato - 2013

Keywords

  • OPMD
  • Pax7

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