HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ryan, M. M. Articles by Beggs, A. H. Search for Related Content PubMed PubMed Citation Articles by Ryan, M. M. Articles by Beggs, A. H. Related Collections Medical care Muscle disease

Clinical course correlates poorly with muscle pathology in nemaline myopathy

From the Department of Neurology (Dr. Ryan), Genetics Division (Drs. Ryan, Sanoudou, and Beggs, and C.D. Strickland and C. Midgett), and Department of Neuropathology (Dr. De Girolami), Children’s Hospital, Boston; Neurogenetics Research Unit (Drs. Ryan and North, and B. Ilkovski and C. Schnell), Children’s Hospital at Westmead (Royal Alexandra Hospital for Children), Sydney; Neuromuscular Disease and Neurorehabilitation (Dr. Iannaccone), Texas Scottish Rite Hospital for Children (R. Houston and D. Muirhead), UT Southwestern Medical Center, Dallas, TX; State Neuropathology Service (Dr. Dennett), Department of Pathology, University of Melbourne, Victoria; Department of Neurology (Dr. Shield), The Royal Children’s Hospital, Victoria, Australia; Harvard Medical School (Drs. De Girolami and Beggs), Boston, MA; Australian Neuromuscular Research Institute (Dr. Laing), QEII Medical Centre, Nedlands, Western Australia; and Department of Paediatrics and Child Health (Dr. North), University of Sydney, Australia.

Address correspondence and reprint requests to Dr. A.H. Beggs, Genetics Division, Children’s Hospital, 300 Longwood Ave., Boston, MA 02115; e-mail: beggs{at}rascal.med.harvard.edu

Objective: To report pathologic findings in 124 Australian and North American cases of primary nemaline myopathy.

Methods: Results of 164 muscle biopsies from 124 Australian and North American patients with primary nemaline myopathy were reviewed, including biopsies from 19 patients with nemaline myopathy due to -actin (ACTA1) mutations and three with mutations in -tropomyosin_SLOW (TPM3). For each biopsy rod number per fiber, percentage of fibers with rods, fiber-type distribution of rods, and presence or absence of intranuclear rods were documented.

Results: Rods were present in all skeletal muscles and diagnosis was possible at all ages. Most biopsies contained nemaline bodies in more than 50% of fibers, although rods were seen only on electron microscopy in 10 patients. Rod numbers and localization correlated poorly with clinical severity. Frequent findings included internal nuclei and increased fiber size variation, type 1 fiber predominance and atrophy, and altered expression of fiber type specific proteins. Marked sarcomeric disruption, increased glycogen deposition, and intranuclear rods were associated with more severe clinical phenotypes. Serial biopsies showed progressive fiber size variation and increasing numbers of rods with time. Pathologic findings varied widely in families with multiple affected members.

Conclusions: Very numerous nemaline bodies, glycogen accumulation, and marked sarcomeric disruption were common in nemaline myopathy associated with mutations in skeletal -actin. Nemaline myopathy due to mutations in -tropomyosin_SLOW was characterized by preferential rod formation in, and atrophy of, type 1 fibers. Light microscopic features of nemaline myopathy correlate poorly with disease course. Electron microscopy may correlate better with disease severity and genotype.

This article has been cited by other articles:

				S. Ladha, S. Coons, S. Johnsen, N. Sambuughin, R. Bien-Wilner, and K. Sivakumar Histopathologic Progression and a Novel Mutation in a Child With Nemaline Myopathy J Child Neurol, July 1, 2008; 23(7): 813 - 817. [Abstract] [PDF]

				H. Tajsharghi, M. Ohlsson, C. Lindberg, and A. Oldfors Congenital Myopathy With Nemaline Rods and Cap Structures Caused by a Mutation in the beta-Tropomyosin Gene (TPM2) Arch Neurol, September 1, 2007; 64(9): 1334 - 1338. [Abstract] [Full Text] [PDF]

				C. E. Keller, A. P. Hays, L. P. Rowland, B. Moghadaszadeh, A. H. Beggs, and G. Bhagat Adult-Onset Nemaline Myopathy and Monoclonal Gammopathy Arch Neurol, January 1, 2006; 63(1): 132 - 134. [Abstract] [Full Text] [PDF]

				J. E. Joya, A. J. Kee, V. Nair-Shalliker, M. Ghoddusi, M.-A. T. Nguyen, P. Luther, and E. C. Hardeman Muscle weakness in a mouse model of nemaline myopathy can be reversed with exercise and reveals a novel myofiber repair mechanism Hum. Mol. Genet., November 1, 2004; 13(21): 2633 - 2645. [Abstract] [Full Text] [PDF]

				B. Ilkovski, K. J. Nowak, A. Domazetovska, A. L. Maxwell, S. Clement, K. E. Davies, N. G. Laing, K. N. North, and S. T. Cooper Evidence for a dominant-negative effect in ACTA1 nemaline myopathy caused by abnormal folding, aggregation and altered polymerization of mutant actin isoforms Hum. Mol. Genet., August 15, 2004; 13(16): 1727 - 1743. [Abstract] [Full Text] [PDF]

				C. F. Costa, H. Rommelaere, D. Waterschoot, K. K. Sethi, K. J. Nowak, N. G. Laing, C. Ampe, and L. M. Machesky Myopathy mutations in {alpha}-skeletal-muscle actin cause a range of molecular defects J. Cell Sci., July 1, 2004; 117(15): 3367 - 3377. [Abstract] [Full Text] [PDF]

				D. Sanoudou, J. N. Haslett, A. T. Kho, S. Guo, H. T. Gazda, S. A. Greenberg, H. G. W. Lidov, I. S. Kohane, L. M. Kunkel, and A. H. Beggs Expression profiling reveals altered satellite cell numbers and glycolytic enzyme transcription in nemaline myopathy muscle PNAS, April 15, 2003; 100(8): 4666 - 4671. [Abstract] [Full Text] [PDF]