Cytochrome C oxydase deficiency: SURF1 gene investigation in patients with Leigh syndrome

• Published in: Biochemical and biophysical research communications Vol. 497; no. 4; pp. 1043 - 1048
• Main Authors: Maalej, Marwa, Kammoun, Thouraya, Alila-Fersi, Olfa, Kharrat, Marwa, Ammar, Marwa, Felhi, Rahma, Mkaouar-Rebai, Emna, Keskes, Leila, Hachicha, Mongia, Fakhfakh, Faiza
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.03.2018
• Subjects: Brain - diagnostic imaging; Child; Child, Preschool; Computer Simulation; Cytochrome C oxydase; Cytochrome-c Oxidase Deficiency - enzymology; DNA Mutational Analysis; Electron Transport Complex IV - metabolism; Humans; Leigh Disease - genetics; Leigh syndrome; Magnetic Resonance Imaging; Male; Membrane Proteins - genetics; Mitochondrial Proteins - genetics; Mitochondrial Proton-Translocating ATPases - genetics; Mutation; RNA Splicing; splicing defects; SURF1 gene; Tunisia; Tunisia; Leigh syndrome; Cytochrome C oxydase; splicing defects; SURF1 gene
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2018.02.169

Leigh syndrome (LS) is a rare progressive neurodegenerative disorder occurring in infancy. The most common clinical signs reported in LS are growth retardation, optic atrophy, ataxia, psychomotor retardation, dystonia, hypotonia, seizures and respiratory disorders. The paper reported a manifestation of 3 Tunisian patients presented with LS syndrome. 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. After clinical investigations, three Tunisian patients were tested for mutations in both MT-ATP6 and SURF1 genes by direct sequencing followed by in silico analyses to predict the effects of sequence variation. The result of mutational analysis revealed the absence of mitochondrial mutations in MT-ATP6 gene and the presence of a known homozygous splice site mutation c.516-517delAG in sibling patients added to the presence of a novel double het mutations in LS patient (c.752-18 A > C/c. c.751 + 16G > A). In silico analyses of theses intronic variations showed that it could alters splicing processes as well as SURF1 protein translation. Leigh syndrome (LS) is a rare progressive neurodegenerative disorder occurring in infancy. The most common clinical signs reported in LS are growth retardation, optic atrophy, ataxia, psychomotor retardation, dystonia, hypotonia, seizures and respiratory disorders. The paper reported a manifestation of 3 Tunisian patients presented with LS syndrome. The aim of this study is MT-ATP6 and SURF1 genes screening in Tunisian patients affected with classical Leigh syndrome and the computational investigation of the effect of detected mutations on its structure and functions. After clinical investigations, three Tunisian patients were tested for mutations in both MT-ATP6 and SURF1 genes by direct sequencing followed by in silico analysis to predict the effects of sequence variation. The result of mutational analysis revealed the absence of mitochondrial mutations in MT-ATP6 gene and the presence of a known homozygous splice site mutation c.516-517delAG in sibling patients added to the presence of a novel double het mutations in LS patient (c.752-18 A>C/ c.751+16G>A). In silico analysis of theses intronic vaiations showed that it could alters splicing processes as well as SURF1 protein translation. •We reported 3 patients with LEIGH syndrome associated with SURF1 gene mutations.•The c.516-517delAG mutation was reported in a Tunisian family.•Two novel intronic variations c.751+16G>A and c.752-18 A>C were reported in an isolated case.