| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
From the Department of Molecular Genetics and Biochemistry (Drs. Scacheri and Hoffman), University of Pittsburgh School of Medicine, PA; Research Center for Genetic Medicine (Drs. Hoffman and Semino–Mora, and A. Senchak), Children’s National Medical Center, George Washington University, Washington, DC; Centre for Neuromuscular and Neurological Disorders (Drs. Davis and Laing), University of Western Australia; and Department of Neurology (Drs. Vedanarayanan and Subramony), University of Mississippi Medical Center, Jackson.
Address correspondence and reprint requests to Dr. S.H. Subramony, University of Mississippi Medical Center, Department of Neurology, 2500 N. State Street, Jackson, MS 39216; e-mail: s_h_s{at}hotmail.com
BACKGROUND: Central core disease (CCD) and nemaline rod myopathy are generally considered two genetically and histologically distinct disorders. CCD is defined by the presence of well-demarcated round cores within most myofibers. Nemaline rod myopathy is distinguished by the presence of characteristic nemaline bodies within myofibers. The simultaneous occurrence of both cores and rods in the same muscle biopsy has been described, but no gene mutations have been reported yet for this condition.
OBJECTIVE: To describe a family containing 16 affected individuals in six generations with an autosomal dominant congenital myopathy that shows clinical and histologic features of both CCD and nemaline myopathy, and to determine the genetic etiology and protein composition of the cores/rods in this family.
METHODS AND RESULTS: The results of linkage analyses excluded involvement of the two autosomal dominant nemaline myopathy loci on chromosome 1, but were consistent with a localization of the disease gene at the CCD locus on chromosome 19q13.1 (ryanodine receptor). SSCP analysis and DNA sequencing identified a novel Thr4637Ala mutation in the transmembrane region of the ryanodine receptor protein. Immunofluorescence studies of patient muscle biopsies showed the central cores to stain for ryanodine receptor.
CONCLUSIONS: These data suggest that the occurrence of nemaline bodies can be a secondary feature of CCD, and that genetic studies on previously reported core/rod families should be targeted to the ryanodine receptor locus. The results of the immunofluorescence studies suggest that the cores contain excess abnormal ryanodine receptor protein.
This article has been cited by other articles:
|
|
 |
|
  N. B. Romero, V. -L. Lehtokari, S. Quijano-Roy, N. Monnier, K. G. Claeys, R. Y. Carlier, N. Pellegrini, D. Orlikowski, A. Barois, N. G. Laing, et al. CORE-ROD MYOPATHY CAUSED BY MUTATIONS IN THE NEBULIN GENE Neurology, October 6, 2009; 73(14): 1159 - 1161. [Full Text] [PDF]
|
|
|
|
 |
|
 W. Klingler, H. Rueffert, F. Lehmann-Horn, T. Girard, and P. M. Hopkins Core Myopathies and Risk of Malignant Hyperthermia Anesth. Analg., October 1, 2009; 109(4): 1167 - 1173. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. H. Goebel Congenital Myopathies in the New Millennium J Child Neurol, February 1, 2005; 20(2): 94 - 101. [Abstract] [PDF]
|
|
|
|
 |
|
 A M Kaindl, F Ruschendorf, S Krause, H-H Goebel, K Koehler, C Becker, D Pongratz, J Muller-Hocker, P Nurnberg, G Stoltenburg-Didinger, et al. Missense mutations of ACTA1 cause dominant congenital myopathy with cores J. Med. Genet., November 1, 2004; 41(11): 842 - 848. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ducreux, F. Zorzato, C. Muller, C. Sewry, F. Muntoni, R. Quinlivan, G. Restagno, T. Girard, and S. Treves Effect of Ryanodine Receptor Mutations on Interleukin-6 Release and Intracellular Calcium Homeostasis in Human Myotubes from Malignant Hyperthermia-susceptible Individuals and Patients Affected by Central Core Disease J. Biol. Chem., October 15, 2004; 279(42): 43838 - 43846. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. M. P. Gommans, M. Davis, K. Saar, M. Lammens, F. Mastaglia, P. Lamont, G. van Duijnhoven, H. J. ter Laak, A. Reis, O. J. M. Vogels, et al. A locus on chromosome 15q for a dominantly inherited nemaline myopathy with core-like lesions Brain, July 1, 2003; 126(7): 1545 - 1551. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Monnier, A. Ferreiro, I. Marty, A. Labarre-Vila, P. Mezin, and J. Lunardi A homozygous splicing mutation causing a depletion of skeletal muscle RYR1 is associated with multi-minicore disease congenital myopathy with ophthalmoplegia Hum. Mol. Genet., May 15, 2003; 12(10): 1171 - 1178. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Davis, R. Brown, A. Dickson, H. Horton, D. James, N. Laing, R. Marston, M. Norgate, D. Perlman, N. Pollock, et al. Malignant hyperthermia associated with exercise-induced rhabdomyolysis or congenital abnormalities and a novel RYR1 mutation in New Zealand and Australian pedigrees Br. J. Anaesth., April 1, 2002; 88(4): 508 - 515. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Tilgen, F. Zorzato, B. Halliger-Keller, F. Muntoni, C. Sewry, L. M. Palmucci, C. Schneider, E. Hauser, F. Lehmann-Horn, C. R. Muller, et al. Identification of four novel mutations in the C-terminal membrane spanning domain of the ryanodine receptor 1: association with central core disease and alteration of calcium homeostasis Hum. Mol. Genet., December 1, 2001; 10(25): 2879 - 2887. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Monnier, N. B. Romero, J. Lerale, P. Landrieu, Y. Nivoche, M. Fardeau, and J. Lunardi Familial and sporadic forms of central core disease are associated with mutations in the C-terminal domain of the skeletal muscle ryanodine receptor Hum. Mol. Genet., October 1, 2001; 10(22): 2581 - 2592. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Avila, J. J. O'Brien, and R. T. Dirksen Excitation-contraction uncoupling by a human central core disease mutation in the ryanodine receptor PNAS, March 27, 2001; 98(7): 4215 - 4220. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
