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Defining the importance of mitochondrial gene defects in maternally inherited diabetes by sequencing the entire mitochondrial genome

Lookup NU author(s): Dr Stephen Lynn, Geoffrey Taylor, Dr Theresa Wardell, Professor Patrick Chinnery, Emeritus Professor Doug Turnbull, Professor Mark Walker


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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 A3249G tRNA(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 glutantic 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.

Publication metadata

Author(s): Wardell TM; Walker M; Taylor GA; Chinnery PF; Lynn S; Turnbull DM; Choo-Kang ATW; Daly ME; Sihota SS

Publication type: Article

Publication status: Published

Journal: Diabetes

Year: 2002

Volume: 51

Issue: 7

Pages: 2317-2320

ISSN (print): 0012-1797

ISSN (electronic): 1939-327X

Publisher: American Diabetes Association


DOI: 10.2337/diabetes.51.7.2317


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