title: 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: UPMC Université Pierre et Marie Curie, Institut de Myologie, Paris, France.
authors: Teresa
authors: T
authors: Gidaro
authors: Elisa
authors: E
authors: Negroni
authors: Sophie
authors: S
authors: Perié
authors: Massimiliano
authors: M
authors: Mirabella
authors: Jeanne
authors: J
authors: Lainé
authors: Jean
authors: J
authors: Lacau St Guily
authors: Gillian
authors: G
authors: Butler-Browne
authors: Vincent
authors: V
authors: Mouly
authors: Capucine
authors: C
authors: Trollet
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001284:Atrophy / Q000473:pathology; D005260:Female; D005355:Fibrosis / Q000473:pathology; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D008875:Middle Aged; D039141:Muscular Dystrophy, Oculopharyngeal / Q000378:metabolism / Q000473:pathology*; D051763:PAX7 Transcription Factor / Q000096:biosynthesis*; D010609:Pharyngeal Muscles / Q000378:metabolism / Q000473:pathology*
chemical_list: D051763:PAX7 Transcription Factor; C497321:PAX7 protein, human