Leigh syndrome French Canadian (LSFC) is a recessive disease caused by mutations in the LRPPRC gene (leucine-rich pentatricopeptide repeat containing protein).
SURF1-mutations were identified in three out of four cases with Leigh syndrome while a mutation in the mitochondrial tRNA (trp) gene was identified in the fourth.
SURF1 gene mutations are the most common cause of Leigh syndrome (LS), a rare progressive neurodegenerative disorder of infancy, characterized by symmetric necrotizing lesions and hypervascularity in the brainstem and basal ganglia, leading to death before the age of 4 years.
TACO1 analysis showed no mutations in 17 patients with juvenile-onset Leigh syndrome and isolated COX or combined respiratory chain deficiency, indicating that TACO1 mutations are a rare cause of Leigh syndrome.
SURF1 gene mutations cause a severe COX deficiency manifesting as the Leigh syndrome in humans, whereas in mice SURF1(-/-) knockout leads only to a mild COX defect.
IARS2 (OMIM 612801) encodes the mitochondrial isoleucine-tRNA synthetase which belongs to the class-I aminoacyl-tRNA synthetase family, and has been implicated in CAGSSS and a form of Leigh syndrome.
MT-ATP6 is associated with some cases of Leigh disease; clinical outcomes in our cohort ranged from death from neurodegenerative disease in early childhood to clinically and developmentally normal after several years of follow-up.