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Complex Neurologic Syndrome Associated With the G1606A Mutation of Mitochondrial DNA
Sabrina Sacconi, MD;
Leonardo Salviati, MD;
Clifton Gooch, MD;
Eduardo Bonilla, MD;
Sara Shanske, PhD;
Salvatore DiMauro, MD
Arch Neurol. 2002;59:1013-1015.
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.
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).
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