title: Electron microscopy in myofibrillar myopathies reveals clues to the mutated gene.
abstract: We studied the ultrastructural characteristics in patients with myofibrillar myopathy (MFM) and differentiated between MFM-subtypes using electron microscopic (EM) findings. The ultrastructural findings in 19 patients with different genetically proven MFMs (9 desmin, 5 alphaB-crystallin, 3 ZASP, 2 myotilin) were analyzed. In one ZASPopathy, we additionally performed an immunoEM study, using antibodies against desmin, alphaB-crystallin, ZASP and myotilin. The ultrastructural findings in desminopathies and alphaB-crystallinopathies were very similar and consisted of electrondense granulofilamentous accumulations and sandwich formations. They differed in the obvious presence of early apoptotic nuclear changes in alphaB-crystallinopathies. ZASPopathies were characterized by filamentous bundles (labeled with the myotilin antibody on immunoEM), and floccular accumulations of thin filamentous material. Tubulofilamentous inclusions in sarcoplasm and myonuclei in combination with filamentous bundles were characteristic for myotilinopathies. We conclude that MFMs ultrastructural findings can direct diagnostic efforts towards the causal gene mutated, and that EM should be included in the diagnostic workup of MFMs.
authors.affiliation: Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, 47-83, Boulevard de l'Hôpital, 75651 Paris, Cedex 13, France. k.claeys@institut-myologie.org
authors.forename: K G
authors.initials: KG
authors.lastname: Claeys
authors.forename: M
authors.initials: M
authors.lastname: Fardeau
authors.forename: R
authors.initials: R
authors.lastname: Schröder
authors.forename: T
authors.initials: T
authors.lastname: Suominen
authors.forename: K
authors.initials: K
authors.lastname: Tolksdorf
authors.forename: A
authors.initials: A
authors.lastname: Behin
authors.forename: O
authors.initials: O
authors.lastname: Dubourg
authors.forename: B
authors.initials: B
authors.lastname: Eymard
authors.forename: T
authors.initials: T
authors.lastname: Maisonobe
authors.forename: T
authors.initials: T
authors.lastname: Stojkovic
authors.forename: G
authors.initials: G
authors.lastname: Faulkner
authors.forename: P
authors.initials: P
authors.lastname: Richard
authors.forename: P
authors.initials: P
authors.lastname: Vicart
authors.forename: B
authors.initials: B
authors.lastname: Udd
authors.forename: T
authors.initials: T
authors.lastname: Voit
authors.forename: G
authors.initials: G
authors.lastname: Stoltenburg
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000368:Aged; D064211:Connectin; D003459:Crystallins / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics; D003893:Desmin / Q000235:genetics; D005260:Female; D006801:Humans; D060588:LIM Domain Proteins; D008297:Male; D008840:Microfilament Proteins; D046529:Microscopy, Electron, Transmission; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009124:Muscle Proteins / Q000235:genetics; D009135:Muscular Diseases / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D009154:Mutation / Q000235:genetics / Q000502:physiology; D009210:Myofibrils / Q000235:genetics* / Q000473:pathology*; D012519:Sarcoplasmic Reticulum / Q000648:ultrastructure
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D064211:Connectin; D003459:Crystallins; D003598:Cytoskeletal Proteins; D003893:Desmin; C120696:LDB3 protein, human; D060588:LIM Domain Proteins; C577290:MYOT protein, human; D008840:Microfilament Proteins; D009124:Muscle Proteins