Abstract
Central core disease (CCD) is a morphologically distinct, autosomal dominant myopathy with variable clinical features. A close association with malignant hypertheria (MH) has been identified. Since MH and CCD genes have been linked to the skeletal muscle ryanodine receptor (RYR1) gene, cDNA sequence analysis was used to search for a causal RYR1 mutation in a CCD individual. The only amino acid substitution found was an Arg2434His mutation, resulting from the substitution of A for G7301. This mutation was linked to CCD with a lod score of 4.8 at a recombinant fraction of 0.0 in 16 informative meioses in a 130 member family, suggesting a causal relationship to CCD.
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References
Shy, G.M. & Magee, K.R. A new congenital non-progressive myopathy. Brain 79, 610–621 (1956).
Patterson, V.H., Hill, T.R., Fletcher, P.J. & Heron, J.R. Central core disease: clinical and pathological evidence within a family. Brain 102, 581–594 (1979).
Ramsey, P.L. & Hensinger, R.N. Congenital dislocation of the hip associated with central core disease. J. Bone joint Surg. 57A, 648–651 (1975).
Dubowitz, V. & Platts, M. Central core disease of muscle with focal wasting. J. Neurol. Neurosurg. Psychiatry. 28, 432–437 (1965).
Shuaib, A., Paasuke, R.T. & Brownell, K.W. Central core disease: clinical features in 13 patients. Medicine 66, 389–396 (1987).
Banker, B.Q. Congenital myopathies. in Myology (eds Engel, A. G. & Banker, B.Q.) 1528–1536 (McGraw Hill, New York, 1986).
Eng, G.D., Epstein, B.S., Engel, W.K., McKay, D.W. & McKay, R. Malignant hyperthermia and central core disease in a child with congenital dislocating hips. Arch. Neurol. 35, 189–197 (1978).
Denborough, M.A., Dennett, X. & Anderson, R. Central core disease and malignant hyperpyrexia. Br. med. J. 1, 272–273 (1973).
Frank, J.P., Harati, Y., Butler, I.J., Nelson, T.E. & Scott, C.I. Central core disease and malignant hyperthermia syndrome. Ann. Neurol. 7, 11–17 (1980).
Brownell, A.K.W. Malignant hyperthermia: relationship to other diseases. Br. J. Anaesth. 60, 303–308 (1988).
Fujii, J. et al. Identification of a mutation in porcine ryanodine receptor associated with malignant hyperthermia. Science 253, 448–451 (1991).
Otsu, K., Khanna, V.K., Archibald, A.L. & MacLennan, D.H. Co-segregation of porcine malignant hyperthermia and a probable causal mutation in the skeletal muscle ryanodine receptor gene in backcross famillies. Genomics 11, 744–750 (1991).
Gillard, E.F. et al. A substitution of cysteine for arginine 614 in the ryanodine receptor is potentially causative of human malignant hyperthermia. Genomics 11, 751–755 (1991).
Gillard, E.F. et al. Polymorphisms and deduced amino acid substitutions in the coding sequence of the ryanodine receptor (RYR1) gene in individuals with malignant hyperthermia. Genomics 13, 1247–1254 (1992).
MacKenzie, A.E. et al. The human ryanodine receptor gene: Its mapping to 19q13.1, placement in a chromosome 19 linkage group, and exclusion as the gene causing myotonic dystrophy. Am. J. hum. Genet. 46, 1082–1089 (1990).
Haan, E.A., Freemantle, C.J., McCure, J.A., Friend, K.L. & Mulley, J.C. Assignment of the gene for central core disease to chromosome 19. Hum. Genet. 86, 187–190 (1990).
Kausch, K. et al. Evidence for linkage of the central core disease locus to the proximal long arm of human chromosome 19. Genomics 10, 765–769 (1991).
Mulley, J.C. et al. Refined genetic localization for central core disease. Am. J. hum. Genet. 52, 398–405 (1993).
Saiki, R.K. et al. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239, 487–491 (1988).
Zorzato, F. et al. Molecular cloning of cDNA encoding human and rabbit forms of the Ca2+ release channel (ryanodine receptor) of skeletal muscle sarcoplasmic reticulum. J. biol. Chem. 265, 2244–2256 (1990).
Takeshima, H. et al. Primary structure and expression from complementary DNA of skeletal muscle ryanodine receptor. Nature 339, 439–445 (1989).
Otsu, K., Phillips, M.S., Khanna, V.K., De Leon, S. & MacLennan, D.H. Refinement of diagnostic assays for a probable causal mutation for porcine and human malignant hyperthermia. Genomics 13, 835–837 (1992).
Walsh, M.P., Brownell, A.K.W., Littmann, V. & Paasuke, R.T. Electrophoresis of muscle proteins is not a method for diagnosis of malignant hyperthermia susceptibility. Anesthesiology 64, 473–479 (1986).
Britt, B.A., The North American Caffeine Halothane Contracture Test, in Malignant Hyperthermia Current Concepts (eds M. A. Nalda Felipe, S. Gottmann & H.J. Khambatta) 53–69 (Normed Verlag, Bad Homburg, 1989).
MacLennan, D.H. et al. Ryanodine receptor gene is a candidate for predisposition to malignant hyperthermia. Nature 343, 559–561 (1990).
McCarthy, T.V. et al. Localization of the malignant hyperthermia susceptibility locus to human chromosome 19q12–13.2. Nature 343, 562–564 (1990).
Hogan, K., Couch, F., Powers, P.A.R. & Gregg, R.G. A cysteine-for arginine substitution (R614C) in the human skeletal muscle calcium release channel cosegregates with malignant hyperthermia. Anesth. Analg. 75, 441–448 (1992).
Levitt, R.C. et al. Evidence for genetic heterogeneity in malignant hyperthermia susceptibility. Genomics 11, 543–547 (1991).
Deufel, T. et al. Evidence for genetic heterogeneity of malignant hyperthermia susceptibility. Am. J. hum. Genet. 50, 1151–1161 (1992).
Caldwell, J.H. & Schaller, K.L. Opening the gates on ion channel disease. Nature Genet. 2, 87–89 (1992).
Otsu, K., Willard, H.F., Khanna, V.K., Zorzato, F., Green, N.M. & MacLennan, D.H. Molecular cloning of cDNA encoding the Ca2+ release channel (ryanodine receptor) of rabbit cardiac muscle sarcoplasmic reticulum. J. biol. Chem. 265, 13472–13483 (1990).
MacLennan, D.H. & Phillips, M.S. Malignant hyperthermia. Science 256, 789–794 (1992).
Carafoli, E. Intracellular calcium homeostasis. A. Rev. Biochem. 56, 395–433 (1987).
Wrogemann, K. & Pena, S.D.J. Mitochondrial calcium overload: a general mechanism for cell necrosis in muscle diseases. Lancet 1, 672–673 (1976).
Miller, S.A., Dykes, S.D. & Polesky, H.F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucl. Acids Res. 16, 1215 (1988).
Chomczynski, P. & Sacchi, N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162, 156–159 (1987).
Wang, A.M., Doyle, M.V. & Mark, D.F. Quantitation of mRNA by the polymerase chain reaction. Proc. natn. Acad. Sci. U.S.A. 86, 9719–9721 (1989).
Ott, J. A computer program for linkage analysis of general human pedigrees. Am. J. hum. Genet. 28, 528–529 (1976).
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Zhang, Y., Chen, H., Khanna, V. et al. A mutation in the human ryanodine receptor gene associated with central core disease. Nat Genet 5, 46–50 (1993). https://doi.org/10.1038/ng0993-46
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DOI: https://doi.org/10.1038/ng0993-46
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