Complex Neurologic Syndrome Associated With the G1606A Mutation of Mitochondrial DNA | Genetics and Genomics | JAMA Neurology | JAMA Network
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June 2002

Complex Neurologic Syndrome Associated With the G1606A Mutation of Mitochondrial DNA

Author Affiliations

From the Departments of Neurology (Drs Sacconi, Salviati, Gooch, Bonilla, Shanske, and DiMauro) and Pathology (Dr Bonilla), Columbia University, New York, NY; Department of Neurology, University of Modena, Modena, Italy (Dr Sacconi); and the Department of Pediatrics, University of Padova, Padova, Italy (Dr Salviati).

Arch Neurol. 2002;59(6):1013-1015. doi:10.1001/archneur.59.6.1013

Objectives  To confirm the pathogenicity of the G-to-A substitution at nucleotide 1606 (G1606A) mutation in the mitochondrial DNA (mtDNA) tRNAVal gene, and to characterize genotype-phenotype correlation.

Patient and Methods  A 37-year-old man since childhood developed a complex clinical picture characterized by hearing loss, migraine, ataxia, seizures, cataracts, retinitis pigmentosa, mental deterioration, and hypothyroidism. Magnetic resonance imaging revealed diffuse calcification of the basal ganglia and cerebral cortical atrophy. Morphologic and biochemical studies of respiratory chain complexes were performed in skeletal muscle. All 22 mitochondrial tRNA genes were screened for mutations by direct sequencing.

Results  Biochemical analysis showed normal activities of respiratory chain enzymes and citrate synthase; morphologic examination showed scattered ragged-red fibers and poor or absent cytochrome c oxidase staining in 10% of the fibers. A heteroplasmic G1606A transition in the mtDNA tRNAVal gene was found. Mutant DNA was 70% of the total in the proband's muscle. The mutation was absent in blood samples and urinary sediment from his healthy brother and mother.

Conclusion  This second patient with the G1606A mutation confirms both the pathogenicity of the mutation and its association with a characteristic complex neurologic phenotype.