Original Investigation
August 2016

Clinical Phenotype and Segregation of Mitochondrial 3243A>G Mutation in 2 Pairs of Monozygotic Twins

Author Affiliations
  • 1Department of Neurology, National Hospital Organization Higashi-ohmi General Medical Center, Higashi-ohmi, Shiga, Japan
  • 2Division of Neurology, Department of Internal Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan
  • 3Department of Internal Medicine, Yabase Chuo Hospital, Kusatsu, Shiga, Japan
  • 4Department of Neurology, Nagano Red Cross Hospital, Nagano, Japan
  • 5Department of Legal Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan
  • 6Division of Pathology and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, Japan
  • 7Departments of Oncology and Space Environmental Medicine, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima, Kagoshima, Japan

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JAMA Neurol. 2016;73(8):990-993. doi:10.1001/jamaneurol.2016.0886

Importance  The regulatory factors explaining the wide spectrum of clinical phenotypes for mitochondrial 3243A>G mutation are not known. Crosstalk between nuclear genes and mitochondrial DNA might be one factor.

Observations  In this case series, we compared 2 pairs of male twins with the mitochondrial 3243 A>G mutation and mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome with a female control patient. One pair of monozygotic twins presented with diabetes and deafness in their 30s, stroke-like episodes in their 40s, and cardiac events and death in their 50s. Another pair of twins presented with deafness and stroke-like episodes in their 20s. The degree of heteroplasmy of 3243A>G mutation in the various tissues and organs was similar in the first pair of twins compared with the control patient.

Conclusions and Relevance  The clinical phenotype and segregation of mitochondrial 3243A>G mutation was similar in monozygotic twins. The onset age and distribution of the symptoms might be regulated by nuclear genes. Our findings might help to predict the clinical course of the surviving twins and afford an opportunity for therapy before the onset of mitochondrial disease, especially for monozygotic twins caused by nuclear transfer with a small amount of nuclear-donor mitochondrial DNA.