title: Skeletal muscle pathology in autosomal dominant Emery-Dreifuss muscular dystrophy with lamin A/C mutations.
abstract: We present our observations on the skeletal muscle pathology of nine cases from seven families of autosomal dominant Emery-Dreifuss muscular dystrophy (ADEDMD) with identified mutations in the lamin A/C gene, aged 2-35 years at the time of biopsy. The severity of pathological change was moderate and the most common features were variation in fibre size (hypertrophy and atrophy), an increase in internal nuclei and smaller diameter fibres with high oxidative enzyme activity. Only one case showed necrosis, which was present in two separate samples taken from the quadriceps and tibialis anterior, at different ages. Immunocytochemistry detected an age-related reduction of laminin beta1 on the muscle fibres in adolescent and adult cases. Antibodies to lamins A and A/C, and emerin did not reveal any detectable differences from controls. Electron microscopy of two out of three cases showed an abnormal distribution of heterochromatin in many fibre nuclei. Our results show that dystrophic changes in skeletal muscle are not a major feature of ADEDMD, and that nuclear abnormalities may be detected with electron microscopy. Immunodetection of reduced laminin beta1 may be a useful secondary marker in adults with this disorder, as immunocytochemistry of lamins is not yet of diagnostic use.
authors.affiliation: Department of Histopathology, Robert Jones & Agnes Hunt Orthopaedic Hospital NHS Trust, Oswestry, UK. c.sewry@ic.ac.uk
authors.forename: C A
authors.initials: CA
authors.lastname: Sewry
authors.forename: S C
authors.initials: SC
authors.lastname: Brown
authors.forename: E
authors.initials: E
authors.lastname: Mercuri
authors.forename: G
authors.initials: G
authors.lastname: Bonne
authors.forename: L
authors.initials: L
authors.lastname: Feng
authors.forename: G
authors.initials: G
authors.lastname: Camici
authors.forename: G E
authors.initials: GE
authors.lastname: Morris
authors.forename: F
authors.initials: F
authors.lastname: Muntoni
mesh_terms: D000293:Adolescent; D000328:Adult; D001707:Biopsy, Needle; D002648:Child; D002675:Child, Preschool; D005260:Female; D005799:Genes, Dominant; D006570:Heterochromatin / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D007223:Infant; D034904:Lamin Type A; D034882:Lamins; D008297:Male; D008854:Microscopy, Electron; D018485:Muscle Fibers, Skeletal / Q000473:pathology / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000473:pathology*; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000235:genetics* / Q000473:pathology*; D022022:Nuclear Pore / Q000473:pathology / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000235:genetics*; D017354:Point Mutation
chemical_list: D006570:Heterochromatin; D034904:Lamin Type A; D034882:Lamins; D009687:Nuclear Proteins