Mitochondrial pathology in inclusion body myositis
Mitochondrial pathology in inclusion body myositis
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DOI：
10.1016/j.nmd.2014.12.010
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发表时间：
2015-04-01
影响因子：
2.8
通讯作者：
Oldfors, Anders
中科院分区：
文献类型：
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作者：
Lindgren, Ulrika;Roos, Sara;Oldfors, Anders
包涵体肌炎（IBM）通常与大量细胞色素c氧化酶（COX）缺乏的肌纤维和获得性线粒体DNA （mtDNA）缺失有关。我们研究了cox缺陷纤维的数量和mtDNA缺失的数量，以及参与mtDNA维持的核基因变异是否可能导致IBM肌肉中mtDNA缺失的发生。纳入26例IBM患者。用形态测定法检测cox缺陷纤维，用qPCR检测mtDNA缺失。Sanger测序分析所有患者的POLG，下一代测序分析6例患者的C10orf2 （Twinkle）、DNA2、MGME1、OPA1、POLG2、RRM2B、SLC25A4和TYMP。肌肉纤维缺乏cox的患者mtDNA缺失的比例明显高于肌肉纤维缺乏cox的患者。我们发现POLG和C10orf2中以前未报道的变异，IBM患者的RRM2B变异频率明显高于对照组。POLG变异在具有许多cox缺陷纤维的IBM患者中更为常见，但差异无统计学意义。我们得出结论，包涵体肌炎中cox缺陷纤维与多个mtDNA缺失有关。在IBM患者中，我们发现了新的和先前报道的对mtDNA维持重要的基因变异，值得进一步研究。(C) 2014 Elsevier B.V.版权所有
Inclusion body myositis (IBM) is usually associated with a large number of cytochrome c oxidase (COX)-deficient muscle fibers and acquired mitochondrial DNA (mtDNA) deletions.We studied the number of COX-deficient fibers and the amount of mtDNA deletions, and if variants in nuclear genes involved in mtDNA maintenance may contribute to the occurrence of mtDNA deletions in IBM muscle.Twenty-six IBM patients were included. COX-deficient fibers were assayed by morphometry and mtDNA deletions by qPCR. POLG was analyzed in all patients by Sanger sequencing and C10orf2 (Twinkle), DNA2, MGME1, OPA1, POLG2, RRM2B, SLC25A4 and TYMP in six patients by next generation sequencing.Patients with many COX-deficient muscle fibers had a significantly higher proportion of mtDNA deletions than patients with few COX-deficient fibers. We found previously unreported variants in POLG and C10orf2 and IBM patients had a significantly higher frequency of an RRM2B variant than controls. POLG variants appeared more common in IBM patients with many COX-deficient fibers, but the difference was not statistically significant.We conclude that COX-deficient fibers in inclusion body myositis are associated with multiple mtDNA deletions. In IBM patients we found novel and also previously reported variants in genes of importance for mtDNA maintenance that warrants further studies. (C) 2014 Elsevier B.V. All rights reserved.