Abstract
An unstable DNA sequence of a gene encoding a protein kinase has been identified as the molecular basis of myotonic dystrophy. The correlation between different symptoms of myotonic dystrophy and the size of this unstable base triplet (CTG)n repeat was investigated in 14 patients. DNA was prepared from whole blood by standard procedures. Detailed clinical, psychological, electrophysiological (quantified measurement of myotonia, electrocardiography) and other laboratory examinations (muscle biopsy in 4 patients, slit lamp examination) were performed. Triplet size correlated significantly with muscular disability and inversely with age at onset of the disease. A greater frequency of mental and gonadal dysfunction could be observed in patients with a larger repeat size. Other symptoms, however, such as cataract, myotonia, gastrointestinal dysfunction and cardiac abnormalities were not correlated with repeat size. Somatic mosaicism with different amplification rates in various tissues might be one possible explanation for the variable phenotypes. Furthermore, other factors such as different expression of the myotonic dystrophy gene might contribute to the clinical variability of the disease at a given triplet size.
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Anvret M, Ahlberg G, Grandell U, Hedberg B, Johnson K, Edstrom L (1993) Larger expansions of the CTG repeat in muscle compared to lymphocytes from patients with myotonic dystrophy. Hum Molec Genet 2: 1397–1400
Ashizawa T, Dubel JR, Harati Y (1993) Somatic instability of CTG repeat in myotonic dystrophy. Neurology 43: 2674–2678
Buxton J, Shelbourne P, Davies J, Jones C, Van Tongeren T, Aslanidis C, Jong P de, Jansen G, Anvret M, Riley B, Williamson R, Johnson K (1992) Detection of an unstable fragment of DNA specific to individuals with myotonic dystrophy. Nature 355: 547–548
Caughey JE, Myrianthopoulos NC (1963) Dystrophia myotonica and related disorders. Thomas, Springfield, Ill.
Censori B, Danni M, Del Pesce M, Provinciali L (1990) Neuropsychological profile in myotonic dystrophy. J Neurol 237: 251–256
Dyken PR, Harper PS (1973) Congenital dystrophia myotonica. Neurology 23: 465–473
Eckardt VF, Nix W (1991) The anal sphincter in patients with myotonic muscular dystrophy. Gastroenterology 100: 424–430
Folstein MF, Folstein SE, McHugh PR (1975) Mini-Mental-State: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12: 189–198
Fu Y-H, Friedman DL, Richards S, Pearlman JA, Gibbs RA, Pizzuti A, Ashizawa T, Perryman MB, Scarlato G, Fenwick RG, Caskey CT (1993) Decreased expression of myotonin-protein kinase messenger RNA and protein in adult form of myotonic dystrophy. Science 260: 235–238
Griggs RC, Wood DS, and the Working Group on the Molecular Defect in Myotonic Dystrophy (1989) Criteria for establishing the validity of genetic recombination in myotonic dystrophy. Neurology 39: 420–421
Harley HG, Brook JD, Rundle SA, Crow S, Reardon W, Buckler AJ, Harper PS, Housman DE, Shaw DJ (1992) Expansion of an unstable DNA region and phenotypic variation in myotonic dystrophy. Nature 355: 545–546
Harley HG, Rundle SA, Reardon W, Myring J, Crow S, Brook JD, Harper PS (1992) Unstable DNA sequence in myotonic dystrophy. Lancet 339: 1125–1128
Harley HG, Rundle SA, MacMillan JC, Myring J, Brook JD, Crow S, Reardon W, Fenton I, Shaw DJ, Harper PS (1993) Size of the unstable CTG repeat sequence in relation to phenotype and parental transmission in myotonic dystrophy. Am J Hum Genet 52: 1164–1174
Harper PS (1989) Myotonic dystrophy. Saunders, London
Hawley RJ, Milner MR, Gottdiener J, Cohen A (1991) Myotonic heart disease: a clinical follow up. Neurology 41: 259–262
Hofmann-Radvanyi H, Lavedan C, Rabes JP, Savoy D, Duros C, Johnson K, Junien C (1993) Myotonic dystrophy — absence of CTG enlarged transcript in congenital forms, and low expression of the normal allele. Hum Molec Genet 2: 1263–1266
Hunter A, Tsilfidis C, Mettler G, Jacob P, Mahadevan M, Surh L, Korneluk R (1992) The correlation of age of onset with CTG trinucleotide repeat amplification in myotonic dystrophy. J Med Genet 29: 774–779
Jennekens FGI, Kate LP ten, Visser M de, Wintzen AR (1991) Diagnostic criteria for Duchenne and Becker muscular dystrophy and myotonic dystrophy. Neuromusc Disord 1: 389–391
Lavedan C, Hofmann-Radvanyi H, Shelbourne P, Rabes J-P, Duros C, Savoy D, Dehaupas I, Luce S, Johnson K, Junien C (1993) Myotonic dystrophy: size- and sex-dependent dynamics of CTG meiotic instability, and somatic mosaicism. Am J Hum Genet 52: 875–883
Lehrl S, Daun H, Schmidt R (1971) Eine Abwandlung des HAWIEWortschatztests als Kurztest zur Messung der Intelligenz Erwachsener. Arch Psychiatr Nervenkr 214: 353–364
Mathieu J, De Braekeleer M, Provost C, Boily C (1992) Myotonic dystrophy: clinical assessment of muscular disability in an isolated population with presumed homogeneous mutation. Neurology 42: 203–208
Olofsson B-O, Forsberg H, Andersson S, Bjerle P, Henrikson A, Wedin I (1988) Electrographic findings in myotonic dystrophy. Br Heart J 59: 47–52
Penrose LS (1948) The problem of anticipation in pedigrees of dystrophia myotonica. Ann Eugen (Lond) 14: 125–232
Perini GI, Colombo G, Armani M, Pellegrini A, Ermani M, Miotti M, Angelini C (1989) Intellectual impairment and cognitive evoked potentials in myotonic dystrophy. J Nerv Ment Dis 177: 750–754
Podczeck A, Graf M, Hief C, Kaltenbrunner W, Nurnberg M, Steinbach K (1993) Electrocardiographic and electrophysiologic findings in patients with myotonic dystrophy. Z Kardiol 82: 474–476
Ptacek LJ, Johnson KJ, Griggs RC (1993) Genetics and physiology of the myotonic muscle disorders. N Engl J Med 328: 482–489
Raven JC (1941) Standardisation of progressive matrices. Br J Med Psychol 19: 137–150
Ricker K, Lehmann-Horn F, Moxley RT (1990) Myotonia fluctuans. Arch Neurol 47: 268–272
Sabouri LA, Mahadevan MS, Narang M, Lee DSC, Surh LC, Korneluk RG (1993) Effect of the myotonic dystrophy (DM) mutation on mRNA levels of the DM gene. Nature Genetics 4: 233–238
30.Thornton CA, Johnson K, Moxley RT (1994) Myotonic dystrophy patients have larger CTG expansions in skeletal muscle than in leukocytes. Ann Neurol 35: 104–107
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Jaspert, A., Fahsold, R., Grehl, H. et al. Myotonic dystrophy: Correlation of clinical symptoms with the size of the CTG trinucleotide repeat. J Neurol 242, 99–104 (1995). https://doi.org/10.1007/BF00887824
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DOI: https://doi.org/10.1007/BF00887824