FULMINANT LEIGH-SYNDROME AND SUDDEN UNEXPECTED DEATH IN A FAMILY WITHTHE T9176C MUTATION OF THE MITOCHONDRIAL ATPASE-6-GENE

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