Abstract:
:We have identified a new mutation in mtDNA, involving tRNALeu(CUN) in a patient manifesting an isolated skeletal myopathy. This heteroplasmic A-->G transition at position 12320 affects the T psi C loop at a conserved site and was not found in 120 controls. Analysis of cultured fibroblasts, white blood cells/platelets, and skeletal muscle showed that only skeletal muscle contained the mutation and that only this tissue demonstrated a biochemical defect of respiratory-chain activity. In a series of four muscle-biopsy specimens taken over a 12-year period, there was a gradual increase, from 70% to 90%, in the overall level of mutation, as well as a marked clinical deterioration. Single-fiber PCR confirmed that the proportion of mutant mtDNA was highest in cytochrome c oxidase-negative fibers. This study, which reports a mutation involving tRNALeu(CUN), demonstrates clearly that mtDNA point mutations can accumulate over time and may be restricted in their tissue distribution. Furthermore, clinical deterioration seemed to follow the increase in the level of mutation, although, interestingly, the appearance of fibers deficient in respiratory-chain activity showed a lag period.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Weber K,Wilson JN,Taylor L,Brierley E,Johnson MA,Turnbull DM,Bindoff LAsubject
Has Abstractpub_date
1997-02-01 00:00:00pages
373-80issue
2eissn
0002-9297issn
1537-6605journal_volume
60pub_type
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journal_title:American journal of human genetics
pub_type: 杂志文章
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
pub_type: 杂志文章
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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更新日期:1993-04-01 00:00:00
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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doi:
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/378241
更新日期:2003-09-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/320105
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abstract::Low bone mineral density (BMD) is a major risk factor for osteoporotic fracture. Studies of BMD in families and twins have shown that this trait is under strong genetic control. To identify regions of the genome that contain quantitative trait loci (QTL) for BMD, we performed independent genomewide screens, using two ...
journal_title:American journal of human genetics
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1992-03-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302873
更新日期:2000-04-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/375039
更新日期:2003-05-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/318198
更新日期:2001-02-01 00:00:00
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1997-05-01 00:00:00
abstract::Genome-wide association studies are routinely conducted to identify genetic variants that influence complex disorders. It is well known that failure to properly account for population or pedigree structure can lead to spurious association as well as reduced power. We propose a method, ROADTRIPS, for case-control assoc...
journal_title:American journal of human genetics
pub_type: 杂志文章
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更新日期:2010-02-12 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章,meta分析
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journal_title:American journal of human genetics
pub_type: 杂志文章
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更新日期:2006-02-01 00:00:00
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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更新日期:1991-10-01 00:00:00
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journal_title:American journal of human genetics
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更新日期:1993-03-01 00:00:00