title: The spectrum of pathology in central core disease.
abstract: Central core disease is a congenital myopathy with muscle weakness defined pathologically by the presence of extensive areas in muscle fibres that are devoid of oxidative enzyme activity. The gene responsible has been shown to be the ryanodine receptor 1 on chromosome 19q13 and mutations have now been identified in several patients. Some cases with the morphological defect remain molecularly undefined, particularly those studied before molecular studies were available. We have studied three families with congenital onset, each with a dominantly inherited mutation in a C-terminal exon of the ryanodine receptor 1. They illustrate the spectrum of pathology that can be observed in patients with the myopathic features of central core disease. We show that extensive fibrosis and fat may be present, type 1 fibre uniformity may occur in the absence of cores; cores may be central or peripheral, single or multiple; and that an appearance of multiple focal minicores might cause a diagnostic pathological dilemma. In addition, we show the value of immunocytochemistry in identifying cores, in particular the use of antibodies to desmin and gamma-filamin.
authors.affiliation: Department of Histopathology and the Neuromuscular Centre, Robert Jones and Agnes Hunt Orthopaedic & District Hospital, NHS Trust, SY10 7AG, Oswestry, UK. c.sewry@ic.ac.uk
authors.forename: C A
authors.initials: CA
authors.lastname: Sewry
authors.forename: C
authors.initials: C
authors.lastname: Müller
authors.forename: M
authors.initials: M
authors.lastname: Davis
authors.forename: J S M
authors.initials: JS
authors.lastname: Dwyer
authors.forename: J
authors.initials: J
authors.lastname: Dove
authors.forename: G
authors.initials: G
authors.lastname: Evans
authors.forename: R
authors.initials: R
authors.lastname: Schröder
authors.forename: D
authors.initials: D
authors.lastname: Fürst
authors.forename: T
authors.initials: T
authors.lastname: Helliwell
authors.forename: N
authors.initials: N
authors.lastname: Laing
authors.forename: R C M
authors.initials: RC
authors.lastname: Quinlivan
mesh_terms: D000328:Adult; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D003285:Contractile Proteins / Q000378:metabolism; D005260:Female; D064448:Filamins; D008040:Genetic Linkage; D006416:Hematoxylin; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D009154:Mutation; D020512:Myopathy, Central Core / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D009246:NADH Tetrazolium Reductase / Q000378:metabolism; D010375:Pedigree; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics; D038203:alpha-Crystallin B Chain / Q000378:metabolism
chemical_list: D003285:Contractile Proteins; D064448:Filamins; D008840:Microfilament Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D038203:alpha-Crystallin B Chain; D009246:NADH Tetrazolium Reductase; D006416:Hematoxylin