By performing whole-exome sequencing in a girl affected by Leigh syndrome and her parents, we identified two heterozygous missense variants (p.Tyr110Cys and p.Val569Met) in the carnitine acetyltransferase (CRAT) gene, encoding an enzyme involved in the control of mitochondrial short-chain acyl-CoA concentrations.
Collectively, these findings demonstrate that downregulation of renal TNF production in response to LS conditions contributes to the regulation of sodium chloride reabsorption via an NKCC2B-dependent mechanism.
Mice lacking the mitochondrial complex I (CI) subunit Ndufs4 ( Ndufs4<sup>-/-</sup>) develop a fatal progressive encephalopathy and serve as a model for Leigh syndrome, the most common mitochondrial disease in children.
We previously showed that breathing chronic, continuous hypoxia can prevent and even reverse neurological disease in the Ndufs4 knockout (KO) mouse model of complex I (CI) deficiency and Leigh syndrome.
A popular mouse model of mitochondrial disease that lacks NADH:ubiquinone oxidoreductase subunit S4 (NDUFS4), a subunit of mitochondrial complex I, phenocopies many traits of the human disease Leigh syndrome, including the development of optic atrophy.
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.
The m.10191T>C mutation in the mitochondrial DNA gene encoding in the respiratory chain complex I (CI) subunit of MTND3 results in the substitution of a highly conserved amino acid (p.Ser45Pro) within the ND3 protein, leading to CI dysfunction and causing a broad clinical spectrum of disorders that includes LS.
The child was found to have a variant in the MT-ND6 gene (m.14484T>C), most commonly associated with Leber hereditary optic neuropathy, despite a phenotype more closely resembling Leigh syndrome.
Short chain enoyl-CoA hydratase (SCEH) deficiency leads to a severe form of autosomal recessive Leigh syndrome with inevitable neurological decline and early mortality.
FOXRED1 blockage could serve as a new animal model for Leigh syndrome due to defective CI, which echoes damage to corpus striatum and affection of the central dopaminergic system in this disease.
FOXRED1 blockage could serve as a new animal model for Leigh syndrome due to defective CI, which echoes damage to corpus striatum and affection of the central dopaminergic system in this disease.