SURF1, ENCODING A FACTOR INVOLVED IN THE BIOGENESIS OF CYTOCHROME-C-OXIDASE, IS MUTATED IN LEIGH-SYNDROME

Leigh Syndrome (LS) is a severe neurological disorder characterized by bilaterally symmetrical necrotic lesions in subcortical brain regions that is commonly associated with systemic cytochrome c oxidase (COX) deficiency. COX deficiency is an autosomal recessive trait and most pa tients belong to a single genetic complementation group. DNA sequence analysis of the genes encoding the structural subunits of the COX comp lex has failed to identify a pathogenic mutation. Using microcell-medi ated chromosome transfer, we mapped the gene defect in this disorder t o chromosome 9q34 by complementation of the respiratory chain deficien cy in patient fibroblasts. Analysis of a candidate gene (SURF1) of unk nown function revealed several mutations, all of which predict a trunc ated protein. These data suggest a role for SURF1 in the biogenesis of the COX complex and define a new class of gene defects causing human neurodegenerative disease.