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Acta Neuropathologica
Published in: Acta Neuropathologica 3/2009

01-03-2009 | Original Paper

Differential involvement of sarcomeric proteins in myofibrillar myopathies: a morphological and immunohistochemical study

Authors: Kristl G. Claeys, Peter F. M. van der Ven, Anthony Behin, Tanya Stojkovic, Bruno Eymard, Odile Dubourg, Pascal Laforêt, Georgine Faulkner, Pascale Richard, Patrick Vicart, Norma B. Romero, Gisela Stoltenburg, Bjarne Udd, Michel Fardeau, Thomas Voit, Dieter O. Fürst

Published in: Acta Neuropathologica | Issue 3/2009

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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 αB-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 αB-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 α-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 αB-crystallinopathy, and that MFM is not a general disease of the myofibril, but primarily affects a subgroup of stress-responsive Z-disc proteins.
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Metadata
Title
Differential involvement of sarcomeric proteins in myofibrillar myopathies: a morphological and immunohistochemical study
Authors
Kristl G. Claeys
Peter F. M. van der Ven
Anthony Behin
Tanya Stojkovic
Bruno Eymard
Odile Dubourg
Pascal Laforêt
Georgine Faulkner
Pascale Richard
Patrick Vicart
Norma B. Romero
Gisela Stoltenburg
Bjarne Udd
Michel Fardeau
Thomas Voit
Dieter O. Fürst
Publication date
01-03-2009
Publisher
Springer-Verlag
Published in
Acta Neuropathologica / Issue 3/2009
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-008-0479-7

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