Myotonic dystrophy: correlation of clinical symptoms with the size of the CTG trinucleotide repeat

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.