In a random sample of 5000 healthy AJ individuals, the carrier frequency of the NDUFS4 mutation c.462delA was 1 in 1000, suggesting that it should be considered in all AJ patients with Leigh syndrome.
Our study confirms the recent observations that SURF1 is consistently involved in disorders of the mitochondrial respiratory chain in patients with typical Leigh syndrome.
Mutations in surfeit locus protein 1 gene (SURF1) were found in 47 children with Leigh syndrome; 2bp deletion 845-846delCT was found in 89% of independent alleles.
Humans diagnosed with mutations in the gene NDUFS4, encoding a nuclear DNA-encoded subunit of CI (NADH dehydrogenase ubiquinone Fe-S protein 4), typically suffer from Leigh syndrome, a neurodegenerative disease with onset in infancy or early childhood.
Our findings suggest that altered calcium metabolism, apart from severe energy production failure, may also contribute to developing pathological conditions in patients with COX-deficient Leigh disease related to SURF-1 gene mutation.
Mutations in Surf1, a human gene involved in the assembly of cytochrome c oxidase (COX), cause Leigh syndrome, the most common infantile mitochondrial encephalopathy, characterized by a specific COX deficiency.
Genotyping microsatellite DNA markers at putative disease loci in inbred/multiplex families with respiratory chain complex I deficiency allows rapid identification of a novel nonsense mutation (IVS1nt -1) in the NDUFS4 gene in Leigh syndrome.
We discuss the brain MR imaging findings in these three cases along with a literature review on the MR features of previously reported cases of patients with POLG gene mutations and Leigh disease due to SURF1 gene mutations.
The effect on the stability of alternative transcripts of different mutations of the NDUFS4 gene in patients with Leigh syndrome with complex I deficiency is presented.
The study included four patients with Leigh syndrome and SURF1 mutations identified from a cohort of 25 children with Leigh syndrome seen over a period of six years (2006-2012).
The aim of this study is the MT[HYPHEN]ATP6 and SURF1 gene screening in Tunisian patients affected with classical Leigh syndrome and the computational investigation of the effect of detected mutations on its structure and functions by clinical and bioinformatics analyses.
We conclude that, although mtDNA mutations are considered to be rare in LS with COX deficiency, the T 5537i mutation should be screened for in cases of LS with COX deficiency when SURF1 gene mutations have been excluded, especially when complex I activity is also decreased.
A constant and similar assembly defect of mitochondrial respiratory chain complex I allows rapid identification of NDUFS4 mutations in patients with Leigh syndrome.
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.