한국인 뒤시엔느형 및 베커형 근디스트로피의 유전자 결손분석

Abstract

Duchenne and Becker muscular dystrophies are X-linked, recessive disease characterized by progressive muscular weakness. Since they are serious disorders for which at present there is no effective treatment, a great deal of emphasis has been given to prevention. To date, however, no precise analysis is available on the mutation of dystrophin gene in Korean patients, thus it is difficult to provide proper genetic counselling.

In this study, we investigated the deletion pattern of dystrophin gene which is the most common cause of the mutation of the dystrophin gene to develop a effective strategy for detecting deletion and to provide a basic data for genetic counselling in Korean patients. We analyzed DNA samples taken from 82 Korean patients from 80 families with clinical picture suspected to having Duchenne or Becker muscular dystrophy using polymerase chain reaction with 19 pairs of primers and Southern hybridization with cDNA 4-5a probe. The results were as follows:

1) At least one DNA frgment could not be amplified from the peripheral blood DNA of the 43 patients from 41 families by polymerase chain reaction. Two pairs of brothers showed same deletion pattern.

2) Exon 49 was the most frequently deleted(20 patients from 19 families). Only one of the 19 amplified fragment was deleted in 27.9%(12/43), more than 1 exon was deleted in the remaining 72.1%(31/43). Deletion were more frequent in central region(34/43) than in the 5' terminal region(9/43).

3) Additional deletion was not found by the Southern hybridization using cDNA 4-5a probe in the patients whom deletion in polymerase chain reaction could not be found.

According to the above results, we can eliminate the need for invasive, expensive, and time consuming procedure such as biopsy or Southern hybridization for about half of patients suspected to having Duchenne or Becker muscular dystrophy. The use of multiplex polymerase chain reaction encompassing the primer pairs corresponding to the exon 17. 45, 49, and 51 would have detected 76.7%(33/43) deletions found in Korean patients. With this observation, our approach to detect deletion will initially be the polymerase chain reaction including the primers of the exon 17, 45, 49, and 51. When a deletion is not found in them, the remaining patients were examined with the rest pairs of primers. If no deletion was found in polymerase chain reaction, then the Southern hybridization with cDNA probe will be carried out.