A study of trinucleotide repeat expansions in myotonic dystrophy

ABSTRACT

PURPOSE: The trinucleotide repeat expansion in the 3' untanslated resion of the gene is known to be the cause of myotonic dystrophy which is one of most common neurodegenerative disorder manifested by myotonia, cataract, mental retardation and even respiratory distress in neonates. The hereditary pattern of myotonic dystrophy shows more severe symptoms and shows earlier onset with successive generations and congenital cases, the most severe form of myotonic dystrophy,. Occurs by maternal transmission. This genetic transmission mode does not follow Mendelian genetic trait. To find the molecular genetic abnormalities of Korean myotonic dystrophy patients, we investigated the general distribution of myotonic dystrophy alleles and compared the results with referred patients. METHODS: During an 8 month study, from June 1995 to February 1996, 5 patients were referred with presumed diagnosis of myotonicdystrophy. Among these patients, four cases were confirmed to have the disease by clinical and electrophysiological findings. We included family members of the studied probands and 50 normal blood donor DNAs were included as controls. The DNAs of the enrolled cases were evaluated by Southern blot. Subsequently, copy numbers of the repeats were determined using PCR amplification. RESULTS: (1) Two peaks were found in the distribution of trinucleotide repeats in the normal Korean population. One peak had 5 copies and the other had 11 to 13 copies. The highest number of copies was 27. (2) Of the referred cases, 4 pedigrees showed typical expanded repeats. (3) The minimum expanded copy number was 55 and we were able to detect the expanded band only by PCR in 2 cases. In other cases, expaded bands were visible by Southern blotting. (4) There were trend of earlier onset of the disease, progressive worsening symptoms and larger expanded bands with successive generations. CONCLUSION: We established the methodology for myotonic dystrophy DNA diagnosis using Southern blot and PCR amplification based on the normal Korean allele distribution. These methods might be useful in genetic counselling and detection of minimally affected myotonic dystrophy patients.