کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8399206 | 1544419 | 2015 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A mutation in MT-TW causes a tRNA processing defect and reduced mitochondrial function in a family with Leigh syndrome
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کلمات کلیدی
NGSOXPHOStRNAIUGRrRNAribosomal ribonucleic acid - اسید ریبونوکلئیک ریبوزومیtransfer ribonucleic acid - انتقال ریبونوکلئیک اسیدMitochondrial disease - بیماری میتوکندریاییNext generation sequencing - توالی نسل بعدیLeigh syndrome - سندرم لیintrauterine growth retardation - عقب ماندگی رشد داخل رحمیOxidative phosphorylation - فسفوریلاسیون اکسیداتیو
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیوفیزیک
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Leigh syndrome (LS) is a progressive mitochondrial neurodegenerative disorder, whose symptoms most commonly include psychomotor delay with regression, lactic acidosis and a failure to thrive. Here we describe three siblings with LS, but with additional manifestations including hypertrophic cardiomyopathy, hepatosplenomegaly, cholestatic hepatitis, and seizures. All three affected siblings were found to be homoplasmic for an m. 5559AÂ >Â G mutation in the T stem of the mitochondrial DNA-encoded MT-TW by next generation sequencing. The m.5559AÂ >Â G mutation causes a reduction in the steady state levels of tRNATrp and this decrease likely affects the stability of other mitochondrial RNAs in the patient fibroblasts. We observe accumulation of an unprocessed transcript containing tRNATrp, decreased de novo protein synthesis and consequently lowered steady state levels of mitochondrial DNA-encoded proteins that compromise mitochondrial respiration. Our results show that the m.5559AÂ >Â G mutation at homoplasmic levels causes LS in association with severe multi-organ disease (LS-plus) as a consequence of dysfunctional mitochondrial RNA metabolism.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Mitochondrion - Volume 25, November 2015, Pages 113-119
Journal: Mitochondrion - Volume 25, November 2015, Pages 113-119
نویسندگان
Rachael M. Duff, Anne-Marie J. Shearwood, Judith Ermer, Giulia Rossetti, Rebecca Gooding, Tara R. Richman, Shanti Balasubramaniam, David R. Thorburn, Oliver Rackham, Phillipa J. Lamont, Aleksandra Filipovska,