Skip Navigation


Brain Advance Access originally published online on January 7, 2004
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
127/2/439    most recent
awh052v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (57)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Selcen, D.
Right arrow Articles by Engel, A. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Selcen, D.
Right arrow Articles by Engel, A. G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Brain, Vol. 127, No. 2, 439-451, 2004
© 2004 Guarantors of Brain
doi: 10.1093/brain/awh052

Myofibrillar myopathy: clinical, morphological and genetic studies in 63 patients

Duygu Selcen, Kinji Ohno and Andrew G. Engel

Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN, USA

Correspondence to: Dr Duygu Selcen, Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA E-mail: Selcen.Duygu{at}mayo.edu

The term myofibrillar myopathy (MFM) was proposed in 1996 as a non-committal term for a pathological pattern of myofibrillar dissolution associated with accumulation of myofibrillar degradation products and ectopic expression of multiple proteins that include desmin, {alpha}B-crystallin ({alpha}BC), dystrophin and congophilic amyloid material. Subsequent studies revealed dominant mutations in desmin and {alpha}BC in some MFM patients, and clinical differences between kinships. We here review the clinical, structural and genetic features of 63 unrelated patients diagnosed as having MFM at the Mayo Clinic between 1977 and 2003. The age of onset was 54 ± 16 years (mean ± SD). Weakness was both proximal and distal in 77% and proximal only in 13%. Cardiomyopathy was diagnosed in 16%. Electro myography revealed a myopathic pattern associated with abnormal electrical irritability; 13 patients had abnormal nerve conduction studies but four of these had long-standing diabetes. The abnormal muscle fibres are best identified in trichrome-stained sections as harbouring amorphous, granular or pleomorphic hyaline structures, and vacuoles containing membranous material. The hyaline structures are strongly congophilic. Semiquantitative analysis in each case indicates that among the abnormal fibres, an average of 90, 75, 75, 70 and 70% abnormally express myotilin, desmin, {alpha}BC, dystrophin and ß-amyloid precursor protein, respectively. Therefore, immunostains for these proteins, and especially for myotilin, are useful adjuncts in the diagnosis of MFM. Electron microscopy shows progressive myofibrillar degeneration commencing at the Z-disk, accumulation of degraded filamentous material and entrapment of dislocated membranous organelles in autophagic vacuoles. In all patients, we searched for mutations in desmin and {alpha}BC, as well as in telethonin, a Z-disk-associated protein, or in syncoilin, which together with plectin links desmin to the Z-disk. Two of the 63 patients carry truncation mutations in the C-terminal domain of {alpha}BC, four carry missense mutations in the head or tail region of desmin, and none carries a mutation in syncoilin or telethonin. Thus, MFM is morphologically distinct but genetically heterogeneous. Further advances in defining the molecular causes of MFM will probably come from linkage studies of informative kinships or from systematic search for mutations in proteins participating in the intricate network supporting the Z-disk.

Key Words: myofibrillar myopathy; Z-disk; desmin; {alpha}B-crystallin; mutation analysis

Abbreviations: {alpha}BC= {alpha}B-crystallin; Aß = ß-amyloid protein; ßAPP = ß-amyloid precursor protein; CDC = cell division cycle; KPI = Kunitz protease inhibitor; LGMD = limb-girdle muscular dystrophy; MFM = myofibrillar myopathy; MUP = motor unit potential; NCAM = neural cell adhesion molecule.

Received August 19, 2003. Revised October 10, 2003. Accepted October 13, 2003.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
C. Geier, K. Gehmlich, E. Ehler, S. Hassfeld, A. Perrot, K. Hayess, N. Cardim, K. Wenzel, B. Erdmann, F. Krackhardt, et al.
Beyond the sarcomere: CSRP3 mutations cause hypertrophic cardiomyopathy
Hum. Mol. Genet., September 15, 2008; 17(18): 2753 - 2765.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
M. Mavroidis, P. Panagopoulou, I. Kostavasili, N. Weisleder, and Y. Capetanaki
A missense mutation in desmin tail domain linked to human dilated cardiomyopathy promotes cleavage of the head domain and abolishes its Z-disc localization
FASEB J, September 1, 2008; 22(9): 3318 - 3327.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
R. A. Kley, Y. Hellenbroich, P. F. M. van der Ven, D. O. Furst, A. Huebner, V. Bruchertseifer, S. A. Peters, C. M. Heyer, J. Kirschner, R. Schroder, et al.
Clinical and morphological phenotype of the filamin myopathy: a study of 31 German patients
Brain, December 1, 2007; 130(12): 3250 - 3264.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
M. Barrachina, J. Moreno, S. Juves, D. Moreno, M. Olive, and I. Ferrer
Target Genes of Neuron-Restrictive Silencer Factor Are Abnormally Up-Regulated in Human Myotilinopathy
Am. J. Pathol., October 1, 2007; 171(4): 1312 - 1323.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
T. Lowe, R. A. Kley, P. F.M. van der Ven, M. Himmel, A. Huebner, M. Vorgerd, and D. O. Furst
The pathomechanism of filaminopathy: altered biochemical properties explain the cellular phenotype of a protein aggregation myopathy
Hum. Mol. Genet., June 1, 2007; 16(11): 1351 - 1358.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
R. Griggs, A. Vihola, P. Hackman, K. Talvinen, H. Haravuori, G. Faulkner, B. Eymard, I. Richard, D. Selcen, A. Engel, et al.
Zaspopathy in a large classic late-onset distal myopathy family
Brain, June 1, 2007; 130(6): 1477 - 1484.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
M. C. Walter, P. Reilich, A. Huebner, D. Fischer, R. Schroder, M. Vorgerd, W. Kress, C. Born, B. G. Schoser, K. H. Krause, et al.
Scapuloperoneal syndrome type Kaeser and a wide phenotypic spectrum of adult-onset, dominant myopathies are associated with the desmin mutation R350P
Brain, June 1, 2007; 130(6): 1485 - 1496.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
C. U. Hubbers, C. S. Clemen, K. Kesper, A. Boddrich, A. Hofmann, O. Kamarainen, K. Tolksdorf, M. Stumpf, J. Reichelt, U. Roth, et al.
Pathological consequences of VCP mutations on human striated muscle
Brain, February 1, 2007; 130(2): 381 - 393.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
X. Wang and J. Robbins
Heart Failure and Protein Quality Control
Circ. Res., December 8, 2006; 99(12): 1315 - 1328.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
B. Ghetti and H. H. Goebel
Frontotemporal dementia: the post-tau era.
Neurology, August 22, 2006; 67(4): 560 - 561.
[Full Text] [PDF]

Home page
 Hum Mol GenetHome page
S. M. Garvey, S. E. Miller, D. R. Claflin, J. A. Faulkner, and M. A. Hauser
Transgenic mice expressing the myotilin T57I mutation unite the pathology associated with LGMD1A and MFM
Hum. Mol. Genet., August 1, 2006; 15(15): 2348 - 2362.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
F. Muntoni, G. Bonne, L. G. Goldfarb, E. Mercuri, R. J. Piercy, M. Burke, R. B. Yaou, P. Richard, D. Recan, A. Shatunov, et al.
Disease severity in dominant Emery Dreifuss is increased by mutations in both emerin and desmin proteins
Brain, May 1, 2006; 129(5): 1260 - 1268.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
M. C. Dalakas
Inflammatory, immune, and viral aspects of inclusion-body myositis
Neurology, January 24, 2006; 66(1_suppl_1): S33 - S38.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
T. Foroud, N. Pankratz, A. P. Batchman, M. W. Pauciulo, R. Vidal, L. Miravalle, H. H. Goebel, L. J. Cushman, B. Azzarelli, H. Horak, et al.
A mutation in myotilin causes spheroid body myopathy
Neurology, December 27, 2005; 65(12): 1936 - 1940.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
H. Bar, N. Mucke, A. Kostareva, G. Sjoberg, U. Aebi, and H. Herrmann
Severe muscle disease-causing desmin mutations interfere with in vitro filament assembly at distinct stages
PNAS, October 18, 2005; 102(42): 15099 - 15104.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
M. Olive, L. G. Goldfarb, A. Shatunov, D. Fischer, and I. Ferrer
Myotilinopathy: refining the clinical and myopathological phenotype
Brain, October 1, 2005; 128(10): 2315 - 2326.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
X. Wang, C. Blagden, J. Fan, S. J. Nowak, I. Taniuchi, D. R. Littman, and S. J. Burden
Runx1 prevents wasting, myofibrillar disorganization, and autophagy of skeletal muscle
Genes & Dev., July 15, 2005; 19(14): 1715 - 1722.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
H. Bar, D. Fischer, B. Goudeau, R. A. Kley, C. S. Clemen, P. Vicart, H. Herrmann, M. Vorgerd, and R. Schroder
Pathogenic effects of a novel heterozygous R350P desmin mutation on the assembly of desmin intermediate filaments in vivo and in vitro
Hum. Mol. Genet., May 15, 2005; 14(10): 1251 - 1260.
[Abstract] [Full Text] [PDF]

Home page
 JWatch NeurologyHome page
The Clinical and Genetic Spectrum of Myofibrillar (Desmin) Myopathy
Journal Watch Neurology, June 11, 2004; 2004(611): 7 - 7.
[Full Text]

Home page
 NeurologyHome page
G. Karpati and M. Sinnreich
A clever road from myopathology to genes: The myotilin story
Neurology, April 27, 2004; 62(8): 1248 - 1249.
[Full Text] [PDF]

Home page
 NeurologyHome page
D. Selcen and A. G. Engel
Mutations in myotilin cause myofibrillar myopathy
Neurology, April 27, 2004; 62(8): 1363 - 1371.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.