A case of a de novo A3243G mutation in mitochondrial DNA in a patient with diabetes and deafness.

A female individual with symptoms of the Maternally Inherited Diabetes and Deafness syndrome (MIDD) was diagnosed positive for the A3243G mutation in her mitochondrial DNA. Heteroplasmy levels were 18% in DNA from leucocytes and 55% in oral mucosa DNA. This finding corroborates the diagnosis of MIDD. Normally, this mutation is present in all the individuals within the maternal lineage of the pedigree. In this particular pedigree the mutation was undetectable in the mother of the proband and her three brothers. Paternity testing using polymorphic chromosomal DNA markers supported the assumed family relationship. We conclude that we are dealing in this proband with the de novo appearance of the A3243G mutation that has reached high heteroplasmy values in at least two tissues within one generation. This observation supports the hypothesis that during embryogenesis mitochondrial DNA goes through a genetic bottleneck with a limited number of segregating units.