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3243 in the tRNA Leu(UUR) gene. Approximatively 1.5% of diabetic patients is found to harbor this mutation when mtDNA is extracted from leucocytes. Never- theless, heteroplasmia hinders the detection of mtDNA point mutations. Pathogenic mutations generally occur in heteroplasmic forms and large variations between various tissues are seen within patients. The amount of mutant mtDNA is higher in muscle than in blood cells, even when diabetic patients have no clinical muscular involvement (1). However, muscle biopsy is an invasive method that cannot be used as a routine examination, especially in diabetic patients. In order to find tissues more informative than blood, we compared the detection rate for pathogenic mtDNA mutations in blood, buccal mucosa and hair follicles. We studied 10 patients harboring the 3243 muta- tion and one patient harboring the T14709C tRNA Glu mutation (2). All patients had either a late onset diabetes mellitus or a history of diabetes in maternal relatives. We determined the relative proportions of mutant and wild-type mtDNA in blood, buccal mucosa and hair follicles as previously described (2). For five of the 3243 positive patients, a muscle biopsy was also available. In our study, all patients had a greater level of mutant mtDNA in muscle than in buccal mucosa, hair follicles and blood (Table 1). Patient 5, a 64-year-old man, presented a combination of diabetes, cardiomyo- pathy, deafness, macular pattern dystrophy, myopathy and chronic diarrhea. This case clearly shows that the percentage of 3243 mutation varies considerably among tissues, with leucocytes being among those having the least heteroplasmy (5%). In our study, the most striking point is that the percentage of mutant mtDNA is higher in buccal mucosa than in leucocytes in ten patients. The last one (patient 2) has a similar level of heteroplasmy in these two cell types. Patient 6, a 53-year-old woman, was suspected of having a respiratory chain defect with a suggestive clinical and family history. In leucocytes, neither mtDNA deletion, nor 3243 point mutation were found. A muscle biopsy was performed. Ragged red fibers were present despite the absence of a clinical myopathy, and the 3243 mutation was identified. Both buccal mucosa and hair follicles were examined subsequently and were found to be positive. Muscle biopsy could have been avoided if this test had been carried out first. In hair follicles, results are more variable, most probably because the percentage of mutated mtDNA is different in various follicles from the same patient (3). The level of heteroplasmy is higher in hair follicles than in blood in 7 patients, lower in 2 cases and similar in 2 patients. The detection rate of 3243 point mutation is low in blood, mainly in elderly patients because heteroplasmy levels of mutant mtDNA decrease in leucocytes upon aging (4, 5). Furthermore, the level of heteroplasmy in blood does not allow the prediction of the age at onset

Searching for A3243G mitochondrial DNA mutation in buccal mucosa in order to improve the screening of patients with mitochondrial diabetes