Multiple deletions of mitochondrial DNA in several tissues of a patient with severe retarded depression and familial progressive external ophthalmoplegia.

Abstract

Multiple deletions of mitochondrial DNA (mtDNA) have recently been reported in familial progressive external ophthalmoplegia (PEO), in a case of progressive encephalomyopathy, and in inherited recurrent myoglobinuria. The inheritance of familial PEO has been autosomal dominant, which indicates that a mutation in an unknown nuclear gene results in several mtDNA deletions of different sizes in these patients. We report a patient with autosomal dominant PEO, whose major clinical symptom, however, was severe retarded depression. The morphological analyses of the tissue samples derived from autopsy showed various abnormalities in the mitochondria in all the tissues studied. The activities of the respiratory chain enzymes encoded by mtDNA were remarkably reduced in the skeletal muscle. The mtDNA analyses confirmed that besides myopathy, this patient had a multisystem disorder with widespread distribution of multiple deletions of mtDNA. The highest percentage of mutated mtDNA was found in the brain, skeletal muscle and the heart, the relative quantity of mutated mtDNA correlating to the severity of the clinical symptoms. (J. Clin. Invest. 1992. 90:61-66.)

Mutant mitochondrial helicase Twinkle causes multiple mtDNA deletions and a late-onset mitochondrial disease in mice

“…A hallmark of the PEO disease is the accumulation of multiple large mtDNA deletions in the patients' postmitotic tissues, the mutant mtDNA reaching up to 60% of total mtDNA in some brain regions and 40% in the skeletal muscle (1,24). We observed accumulation of similar deletions in the corresponding mouse tissues.…”

Syndromic parkinsonism and dementia associated with OPA1 missense mutations

“…However, the striking similarity of both probands from each family (III:7 in Family 1 and III:1 in Family 2) and further recurrence of these features in other individuals suggest that both hypertension and anxiety disorder may be underestimated features in mitochondrial diseases. Previous reports noted depression and anxiety or other psychiatric disturbances in syndromes associated with mtDNA multiple deletions 40, 42…”

“…These features are neither common nor specific to mitochondrial diseases, but they may both have been overlooked to date, because they are frequent in the general population and difficult to relate to mitochondrial dysfunction 40, 41, 42, 43. However, the striking similarity of both probands from each family (III:7 in Family 1 and III:1 in Family 2) and further recurrence of these features in other individuals suggest that both hypertension and anxiety disorder may be underestimated features in mitochondrial diseases.…”

The other, forgotten genome: mitochondrial DNA and mental disorders

“…89 And a segregation analysis suggested multifactorial inheritance in maternally inherited pedigrees and a single major gene in paternally transmitted pedigrees. 90 Comorbidity with mitochondrial diseases Depression frequently shows comorbidity with general disorders including mitochondrial encephalomyopathy [91][92][93][94][95][96][97][98][99][100][101] and there are several reports suggesting a pathogenetic role for mtDNA mutation in mood disorders. 95,99 Suomalainen et al 95 report a family with CPEO caused by multiple deletions of mtDNA.…”