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Differential involvement of sarcomeric proteins in myofibrillar myopathies: a morphological and immunohistochemical study.
- Source :
-
Acta neuropathologica [Acta Neuropathol] 2009 Mar; Vol. 117 (3), pp. 293-307. Date of Electronic Publication: 2009 Jan 17. - Publication Year :
- 2009
-
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.
- Subjects :
- Actins metabolism
Adaptor Proteins, Signal Transducing genetics
Adult
Biopsy
Cohort Studies
Connectin
Desmin genetics
Female
Filamins
Humans
Immunohistochemistry
LIM Domain Proteins
Male
Middle Aged
Muscle Fibers, Skeletal pathology
Muscle, Skeletal metabolism
Muscular Diseases diagnosis
Muscular Diseases genetics
Myofibrils metabolism
Necrosis pathology
Vacuoles pathology
alpha-Crystallin B Chain genetics
Contractile Proteins metabolism
Cytoskeletal Proteins metabolism
DNA-Binding Proteins metabolism
Microfilament Proteins metabolism
Muscle Proteins genetics
Muscle Proteins metabolism
Muscle, Skeletal pathology
Muscular Diseases pathology
Myofibrils pathology
Nuclear Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0533
- Volume :
- 117
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Acta neuropathologica
- Publication Type :
- Academic Journal
- Accession number :
- 19151983
- Full Text :
- https://doi.org/10.1007/s00401-008-0479-7