title: Complex neurologic syndrome associated with the G1606A mutation of mitochondrial DNA.
abstract: OBJECTIVE
  To confirm the pathogenicity of the G-to-A substitution at nucleotide 1606 (G1606A) mutation in the mitochondrial DNA (mtDNA) tRNA(Val) gene, and to characterize genotype-phenotype correlation.
  
  
  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 tRNA(Val) 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.
  
  
  CONCLUSIONS
  This second patient with the G1606A mutation confirms both the pathogenicity of the mutation and its association with a characteristic complex neurologic phenotype.
authors.affiliation: Department of Neurology, Columbia University, New York, NY, USA.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Sacconi
authors.forename: Leonardo
authors.initials: L
authors.lastname: Salviati
authors.forename: Clifton
authors.initials: C
authors.lastname: Gooch
authors.forename: Eduardo
authors.initials: E
authors.lastname: Bonilla
authors.forename: Sara
authors.initials: S
authors.lastname: Shanske
authors.forename: Salvatore
authors.initials: S
authors.lastname: DiMauro
mesh_terms: D000225:Adenine; D000328:Adult; D001921:Brain / Q000201:enzymology / Q000473:pathology; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D006147:Guanine; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology; D009154:Mutation / Q000235:genetics*; D009422:Nervous System Diseases / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D012343:RNA, Transfer / Q000235:genetics; D013577:Syndrome
chemical_list: D004272:DNA, Mitochondrial; D006147:Guanine; D012343:RNA, Transfer; D000225:Adenine