Three novel SURF-1 mutations in Japanese patients with Leigh syndrome

Abstract 

Leigh syndrome, a severe neurodegenerative disorder, commonly is associated with cytochrome c oxidase deficiency. Recent studies in white patients indicate that SURF-1 gene mutations can cause Leigh syndrome associated with cytochrome c oxidase deficiency. When we measured cytochrome c oxidase activity in cultured lymphoblastoid cells from our Japanese patients with typical Leigh syndrome, three patients demonstrated cytochrome c oxidase deficiency. Three novel mutations of the SURF-1 gene were identified in two of these three patients with cytochrome c oxidase deficiency. All mutations predicted loss of function of the SURF-1 protein; in both patients’ cells, cytochrome c oxidase activity was decreased to less than 20% of the control mean. These results indicate that cultured lymphoblastoid cells are useful for elucidating the etiology of Leigh syndrome, and that loss of function of the SURF-1 gene product can be responsible for Leigh syndrome associated with severe cytochrome c oxidase deficiency in Japanese patients.