MITOCHONDRIAL ENCEPHALOMYOPATHY AND HYPOPARATHYROIDISM ASSOCIATED WITH A DUPLICATION AND A DELETION OF MITOCHONDRIAL DEOXYRIBONUCLEIC-ACID

Diabetes mellitus is the most frequent endocrinopathy associated with mitochondrial disorders, particularly in patients with duplications of mitochondrial DNA (mtDNA). Although hypoparathyroidism has also been described in mitochondrial diseases, there have been few molecular stu dies in these cases, most of which identified the presence of single m tDNA deletions in the patients' tissues. We studied muscle DNA of a 12 -yr-old patient with incomplete Kearns-Sayre syndrome and hypoparathyr oidism. Southern analysis showed that muscle DNA contained three popul ations of mtDNA: wild type (26%), deleted (65%), and duplicated (9%). To determine the sequence of the breakpoint region from deleted and du plicated mtDNA independently, we isolated the deleted and duplicated m tDNA by gel fractionation of a PstI-digested total DNA. The breakpoint was located at mtDNA positions 5788 and 15448 for both duplicated and deleted molecules. Our study reinforces the concept that endocrinopat hies other than diabetes can be associated with a duplication of mtDNA and gives additional support to the hypothesis that the duplication a nd deletion of mtDNA are generated from the same recombination event.