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For any mitochondrial DNA (mtDNA) mutation, the ratio of mutant to wild-type mtDNA (% heteroplasmy) varies across tissues, with low levels in leukocytes and high levels in postmitotic tissues (e.g., skeletal muscle). Direct sequencing is the gold-standard method used to detect novel mutations, but can only reliably detect % heteroplasmy >25%, which is rare in leukocytes. Therefore, we investigated the role of mtDNA defects in maternally inherited diabetes by first screening for the A3243G [tRNA.sup.Leu(UUR)] mutation by restriction assay, followed by sequencing of the entire mitochondrial genome using skeletal muscle derived mtDNA. A total of 28 patients had maternally inherited diabetes either alone (group 1, n = 17) or with one or more additional features of mitochondrial disease, including bilateral sensori-neural deafness and neuromuscular disease (group 2, n = 11). Three patients (all from group 2) carried the A3243G mutation. Skeletal muscle mtDNA from eight group 1 patients and six more group 2 patients was sequenced. No pathogenic mutations were found in the group 1 patients, while two patients from group 2 had mutations at positions 12258 and 14709 in the tRNA serine and glutamic acid genes, respectively. We conclude, therefore, that screening for mtDNA mutations should be considered in patients with maternally inherited diabetes, but only when additional features of mitochondrial disease are present. Diabetes 51:2317-2320, 2002, It is well recognized that in some families diabetes follows a maternal inheritance pattern, and that there is an excess of maternal transmission in type 2 diabetes. As mitochondrial DNA [...]

Defects of mitochondrial DNA (mtDNA) have recently been recognized as a cause of diabetes (1,2). The mitochondrial genome is the only extrachromosomal DNA in human cells. It encodes for 13 [...]

To investigate the contribution of inherited biochemical defects to the peripheral insulin resistance of type 2 diabetes, we studied cultured skeletal muscle from 10 insulin-resistant nondiabetic first-degree relatives of type [...]

Many mitochondrial DNA (mtDNA) mutations have been associated with diabetes mellitus (DM), in which impaired insulin secretion is a key feature. Therefore, the pancreatic [Beta]-cell is a likely target for [...]

Recent studies suggest that genetic variation in the calpain 10 gene is associated with type 2 diabetes mellitus in Mexican American and other populations. We investigated whether G/A (UCSNP-43) and [...]

Skeletal muscle insulin resistance (IR) is a feature of non-diabetic 1st degree relatives of Type 2 diabetic families. We investigated the genetic basis of this using a skeletal muscle culture [...]

The true role of mitochondrial DNA (mtDNA) mutations in the pathogenesis of diabetes remains uncertain. What is clear, however, is that mitochondrial diabetes is recognised as an important subgroup of [...]

The m.3243A>G mitochondrial DNA mutation is well known to be associated with deafness and diabetes, and patients presenting with these clinical features are routinely screened for this mutation. We wanted [...]