Large-scale mitochondrial DNA deletions in patients with CPEO syndrome in Taiwan
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文摘
We investigated the mtDNA mutations in muscle biopsies obtained from eighteen Chinese patients in Taiwan with chronic progressive external ophthalmoplegia by Southern blot analysis, long-range PCR and primer-shift PCR techniques, and direct DNA sequencing. The results showed that a common 4,977 bp deletion was present in the muscle of eight of these patients and the proportions of the mutant mtDNA were between 46 % and 90 % , respectively. One of them was found to harbor a 4,366 bp deletion between np 9579 and np 13944 (or between np 9587 and np 13952) of mtDNA, and the breakpoints were flanked by a 9-bp direct repeat of 5′-TTAGGGGAT-3′. Another one had a novel 8,695 bp deletion between np 6928 and np 15122 of mtDNA. Interestingly, one out of the 18 CPEO patients was found to have the A3243G point mutation. Seven of these CPEO patients did not harbor any of the above deletions or point mutations of mtDNA. In general, the patients who harbored higher proportions of the 4,977 bp deleted or other type of mutant mtDNA tended to exhibit more severe clinical phenotype and earlier onset of the disease. These results suggest that about 50 % of the Chinese patients with CPEO syndrome are associated with or caused by the large-scale deletion of mtDNA and that the 4,977 bp deletion is the most dominant mtDNA mutation in Taiwanese patients with CPEO syndrome. Moreover, the findings that the A3243G transition of mtDNA was present in the muscle biopsies of one CPEO patient indicate that CPEO syndrome may have multiple etiological factors and that different types of mtDNA mutations may lead, by the same or different mechanisms, to the same mitochondrial disease.