Homoplastic A12,753G mitochondrial DNA mutation in a Hungarian family

A 42-year-old male patient with clinical symptoms resembling multiple scler osis but showing slight unusual myopathic features was referred to our clin ic. Analysis of mtDNA isolated from the patient's skeletal muscle revealed two homoplastic Pvu II restriction sites instead of the usual single one. A t the same lime, digestion of the DNA with BamH I and with Sac I resulted i n the normal one and two restriction fragments, respectively. For search of the mutation as the possible background of the patient's disease, serial P CR amplifications were carried out, and the new Pvu II site was tentatively located within the 12,352 and 12,914 np. This region of the patient's mtDN A was sequenced and an A to G transition at the 12,753 np position was foun d. According to the sequence analysis, this mutation was responsible for ge neration of the new Pvu II restriction site. The mutation caused a modifica tion of the CAA triplet at the 12,751 position to CAG. Since both triplets encode glucamine in the mtDNA, the mutation could not have been responsible for the patient's disease. The same mutation was identified in the healthy brothers of the patient. Our investigation seems to have recognized a vali ant of the mtDNA in a Hungarian family which has not been revealed so far i n any European haplogroup.