2004
DOI: 10.1093/nar/gkh226
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Biochemical characterization of the mitochondrial tRNASer(UCN) T7511C mutation associated with nonsyndromic deafness

Abstract: We report here the biochemical characterization of the deafness-associated mitochondrial tRNA(Ser(UCN)) T7511C mutation, in conjunction with homoplasmic ND1 T3308C and tRNA(Ala) T5655C mutations using cybrids constructed by transferring mitochondria from lymphoblastoid cell lines derived from an African family into human mtDNA-less (rho degrees ) cells. Three cybrids derived from an affected matrilineal relative carrying the homoplasmic T7511C mutation, exhibited approximately 75% decrease in the tRNA(Ser(UCN)… Show more

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Cited by 119 publications
(113 citation statements)
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References 49 publications
(86 reference statements)
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“…The A406T mutation in the ND4 was not highly conserved, whereas the I175V mutation in the CO2 and the V112M mutation in the ND6 are localized at sites that are highly conserved in human [Anderson et al, 1981], mouse [Bibb et al, 1981], bovine [Gadaleta et al, 1989], and Xenopus [Roe et al, 1985]. There is an increasing evidence showing that the background sequences (haplotype) of the mtDNA modulate the severity and penetrance of the phenotypic expression of pathogenic mtDNA mutation(s) associated with some clinical abnormalities including hearing loss [Guan et al, 1998;Li et al, 2004c] and blindness [Torroni et al, 1997]. Here, the I175V mutation in the CO2 and the V112M mutation in the ND6, showing high evolutionary conservation, may contribute to the phenotypic expression of the T1095C mutation in this patient.…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…The A406T mutation in the ND4 was not highly conserved, whereas the I175V mutation in the CO2 and the V112M mutation in the ND6 are localized at sites that are highly conserved in human [Anderson et al, 1981], mouse [Bibb et al, 1981], bovine [Gadaleta et al, 1989], and Xenopus [Roe et al, 1985]. There is an increasing evidence showing that the background sequences (haplotype) of the mtDNA modulate the severity and penetrance of the phenotypic expression of pathogenic mtDNA mutation(s) associated with some clinical abnormalities including hearing loss [Guan et al, 1998;Li et al, 2004c] and blindness [Torroni et al, 1997]. Here, the I175V mutation in the CO2 and the V112M mutation in the ND6, showing high evolutionary conservation, may contribute to the phenotypic expression of the T1095C mutation in this patient.…”
Section: Resultsmentioning
confidence: 99%
“…First, the subject's DNA fragments spanning the entire mitochondrial 12S rRNA gene or tRNA Ser(UCN) gene were amplified by PCR using oligodeoxynucleotides corresponding to the mitochondrial genome at positions 618-635 and 1988618-635 and -2007618-635 and [Guan et al, 1996Zhao et al, 2004] and 7148-7167 and 8076-8095 [Guan et al, 1998;Li et al, 2004c], respectively. Each fragment was purified and subsequently analyzed by direct sequencing in an ABI 3700 automated DNA sequencer using the Big Dye Terminator Cycle sequencing reaction kit.…”
Section: Methodsmentioning
confidence: 99%
“…In particular, mtDNA mutations at positions 4216 and 13708 labeled as second LHON mutations were implicated to increase the penetrance of the deafness-associated A7445G mutation [Guan et al, 1998], while the ND1 T3308C and tRNA Ala T5655C mutations likely contribute to the higher penetrance of deafness in an African pedigree than Japanese and French families carrying the T7511C mutation [Li et al, 2004c]. Apart from the A1555G and G7444A mutations, 36 variants in this mitochondrial genome, belonging to the Eastern Asian haplogroup D4a [Yao et al, 2002], showed no evolutionary conservation.…”
Section: Discussionmentioning
confidence: 99%
“…A functional study in cybrid cell lines derived from affected individuals in this family has shown that the T7511C mutation leads to ~75% decrease in the tRNA Ser(UCN) level [91]. Furthermore, the T5655C mutation produces ~50% reduction in the tRNA Ala level, and the T3308C mutations causes a significant decrease both in the amount of ND1 mRNA and co-transcribed tRNA Leu(UUR) [91]. It is reasonable that a combination of the T7511C mutation with two other mtDNA variants may lead to significant biochemical defects in mutant cell lines, and may probably account for the high penetrance of hearing loss in this African American family.…”
Section: Mitochondrial Trna Mutations Associated With Nonsyndromic Hementioning
confidence: 99%
“…Interestingly, the homoplasmic ND1 T3308C and tRNA Ala T5655C mutations were found in all maternal members of the African American pedigree [50]. A functional study in cybrid cell lines derived from affected individuals in this family has shown that the T7511C mutation leads to ~75% decrease in the tRNA Ser(UCN) level [91]. Furthermore, the T5655C mutation produces ~50% reduction in the tRNA Ala level, and the T3308C mutations causes a significant decrease both in the amount of ND1 mRNA and co-transcribed tRNA Leu(UUR) [91].…”
Section: Mitochondrial Trna Mutations Associated With Nonsyndromic Hementioning
confidence: 99%