Two new mutations in the MT-TW gene leading to the disruption of the secondary structure of the tRNA^Trp in patients with Leigh syndrome

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• 作者：Emna Mkaouar-Rebai ; Imen Chamkha ; Fatma Kammoun ; Thouraya Kammoun ; Hajer Aloulou ; Mongia Hachicha ; Chahnez Triki ; Faiza Fakhfakh
• 关键词：Leigh syndrome ; Mitochondrial mutations ; Mitochondrial polymorphisms ; MT-TW
• 刊名：Molecular Genetics and Metabolism
• 出版年：2009
• 出版时间：July 2009
• 年：2009
• 卷：97
• 期：3
• 页码：179-184
• 全文大小：934 K

文摘

Leigh syndrome is a progressive neurodegenerative disorder occurring in infancy and childhood characterized in most cases by a psychomotor retardation, optic atrophy, ataxia, dystonia, failure to thrive, seizures and respiratory failure. In this study, we performed a systematic sequence analysis of mitochondrial genes associated with LS in Tunisian patients. We sequenced the encoded complex I units: ND2, ND3, ND4, ND5 and ND6 genes and the mitochondrial ATPase 6, tRNA^Val, tRNA^Leu(UUR), tRNA^Trp and tRNA^Lys genes in 10 unrelated patients with Leigh syndrome. We revealed the presence of 34 reported polymorphisms, nine novel nucleotide variants and two new mutations (T5523G and A5559G) in the tested patients. These two mutations were localized in two conserved regions of the tRNA^Trp and affect, respectively, the D-stem and the T-stem of the mitochondrial tRNA leading to a disruption of the secondary structure of this tRNA. SSP-PCR analysis showed that the T5523G and A5559G mutations were present with respective heteroplasmic rates of 66 % and 43 % . We report here the first mutational screening of mitochondrial mutations in Tunisian patients with Leigh syndrome which described two novel mutations associated with this disorder.