title: Differential involvement of sarcomeric proteins in myofibrillar myopathies: a morphological and immunohistochemical study.
abstract: Myofibrillar myopathies (MFMs) are rare inherited or sporadic progressive neuromuscular disorders with considerable clinical and genetic heterogeneity. In the current study, we have analyzed histopathological and immunohistochemical characteristics in genetically identified MFMs. We performed a morphological and morphometrical study in a cohort of 24 genetically identified MFM patients (12 desmin, 6 alphaB-crystallin, 4 ZASP, 2 myotilin), and an extensive immunohistochemical study in 15 of these patients, using both well-known and novel antibodies directed against distinct compartments of the muscle fibers, including Z-disc and M-band proteins. Our morphological data revealed some significant differences between the distinct MFM subgroups: the consistent presence of 'rubbed-out' fibers in desminopathies and alphaB-crystallinopathies, an elevated frequency of vacuoles in ZASPopathies and myotilinopathies, and the presence of a few necrotic fibers in the two myotilinopathy patients. Immunohistochemistry showed that in MFM only a subset of Z-disc proteins, such as filamin C and its ligands myotilin and Xin, exhibited significant alterations in their localization, whereas other Z-disc proteins like alpha-actinin, myopodin and tritopodin, did not. In contrast, M-band proteins revealed no abnormalities in MFM. We conclude that the presence of 'rubbed-out' fibers are a suggestive feature for desminopathy or alphaB-crystallinopathy, and that MFM is not a general disease of the myofibril, but primarily affects a subgroup of stress-responsive Z-disc proteins.
authors.affiliation: Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. k.claeys@institut-myologie.org
authors.forename: Kristl G
authors.initials: KG
authors.lastname: Claeys
authors.forename: Peter F M
authors.initials: PF
authors.lastname: van der Ven
authors.forename: Anthony
authors.initials: A
authors.lastname: Behin
authors.forename: Tanya
authors.initials: T
authors.lastname: Stojkovic
authors.forename: Bruno
authors.initials: B
authors.lastname: Eymard
authors.forename: Odile
authors.initials: O
authors.lastname: Dubourg
authors.forename: Pascal
authors.initials: P
authors.lastname: Laforêt
authors.forename: Georgine
authors.initials: G
authors.lastname: Faulkner
authors.forename: Pascale
authors.initials: P
authors.lastname: Richard
authors.forename: Patrick
authors.initials: P
authors.lastname: Vicart
authors.forename: Norma B
authors.initials: NB
authors.lastname: Romero
authors.forename: Gisela
authors.initials: G
authors.lastname: Stoltenburg
authors.forename: Bjarne
authors.initials: B
authors.lastname: Udd
authors.forename: Michel
authors.initials: M
authors.lastname: Fardeau
authors.forename: Thomas
authors.initials: T
authors.lastname: Voit
authors.forename: Dieter O
authors.initials: DO
authors.lastname: Fürst
mesh_terms: D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D001706:Biopsy; D015331:Cohort Studies; D064211:Connectin; D003285:Contractile Proteins / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003893:Desmin / Q000235:genetics; D005260:Female; D064448:Filamins; D006801:Humans; D007150:Immunohistochemistry; D060588:LIM Domain Proteins; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism*; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology*; D009135:Muscular Diseases / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D009210:Myofibrils / Q000378:metabolism / Q000473:pathology*; D009336:Necrosis / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism*; D014617:Vacuoles / Q000473:pathology; D038203:alpha-Crystallin B Chain / Q000235:genetics
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D064211:Connectin; D003285:Contractile Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D003893:Desmin; D064448:Filamins; C120696:LDB3 protein, human; D060588:LIM Domain Proteins; C577290:MYOT protein, human; D008840:Microfilament Proteins; D009124:Muscle Proteins; D009687:Nuclear Proteins; C503979:SYNPO2 protein, human; C512114:XIRP1 protein, human; D038203:alpha-Crystallin B Chain