Fulminant Leigh syndrome and sudden unexpected death in a family with the T9176C mutation of the mitochondrial ATPase 6 gene

J Inherit Metab Dis. 1998 Feb;21(1):2-8. doi: 10.1023/a:1005397227996.


We report an Italian family in which the T-to-C point mutation at nucleotide 9176 of the mitochondrial adenosine triphosphate synthetase (mtATPase) 6 gene is associated with an early-onset fulminant form of Leigh syndrome and with sudden unexpected death in two siblings, respectively. Polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing revealed that the mutation was homoplasmic in mitochondrial DNA of the proband. The T9176C mutation changes a highly conserved leucine to a proline in subunit 6 of the mtATPase gene and is maternally inherited, but the maternal relatives are asymptomatic. This point mutation was initially described in two brothers with bilateral striatal necrosis, a milder variant of Leigh syndrome.

Publication types

  • Case Reports

MeSH terms

  • Adenosine Triphosphatases / genetics*
  • Cysteine / genetics
  • DNA, Mitochondrial
  • Humans
  • Infant
  • Leigh Disease / diagnostic imaging
  • Leigh Disease / enzymology
  • Leigh Disease / genetics*
  • Male
  • Mitochondria / enzymology*
  • Mitochondria / genetics
  • Pedigree
  • Point Mutation*
  • Radiography
  • Sudden Infant Death*
  • Threonine / genetics
  • Tomography Scanners, X-Ray Computed


  • DNA, Mitochondrial
  • Threonine
  • Adenosine Triphosphatases
  • Cysteine