Homoplasmic deleterious MT-ATP6/8 mutations in adult patients,Mitochondrion

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Homoplasmic deleterious MT-ATP6/8 mutations in adult patients
Mitochondrion ( IF 3.9 ) Pub Date : 2020-11-01 , DOI: 10.1016/j.mito.2020.08.004
Benoit Rucheton ₁ , Claude Jardel ₁ , Sandrine Filaut ₁ , Maria Del Mar Amador ₂ , Thierry Maisonobe ₃ , Isabelle Serre ₄ , Norma Beatriz Romero ₅ , Sarah Leonard-Louis ₃ , Francis Haraux ₆ , Anne Lombès ₇

Affiliation

To address the frequency of complex V defects, we systematically sequenced MT-ATP6/8 genes in 512 consecutive patients. We performed functional analysis in muscle or fibroblasts for 12 out of 27 putative homoplasmic mutations and in cybrids for four. Fibroblasts, muscle and cybrids with known deleterious mutations underwent parallel analysis. It included oxidative phosphorylation spectrophotometric assays, western blots, structural analysis, ATP production, glycolysis and cell proliferation evaluation. We demonstrated the deleterious nature of three original mutations. Striking gradation in severity of the mutations consequences and differences between muscle, fibroblasts and cybrids implied a likely under-diagnosis of human complex V defects.

中文翻译：

成人患者的同质有害 MT-ATP6/8 突变

为了解决复杂 V 缺陷的频率，我们系统地对 512 名连续患者的 MT-ATP6/8 基因进行了测序。我们在肌肉或成纤维细胞中对 27 个推定的同质突变中的 12 个进行了功能分析，在 cybrids 中对四个进行了功能分析。具有已知有害突变的成纤维细胞、肌肉和胞质体进行了平行分析。它包括氧化磷酸化分光光度测定、蛋白质印迹、结构分析、ATP 生产、糖酵解和细胞增殖评估。我们证明了三个原始突变的有害性质。突变后果的严重程度和肌肉、成纤维细胞和杂种之间的差异的显着分级暗示可能对人类复合体 V 缺陷的诊断不足。

更新日期：2020-11-01

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