Congenital Hypermetabolism and Uncoupled Oxidative Phosphorylation.
Congenital Hypermetabolism and Uncoupled Oxidative Phosphorylation.
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DOI：
10.1056/nejmoa2202949
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发表时间：
2022-10-13
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我们描述了同卵双胞胎男孩的案例，尽管热量摄入过多，但体重仍然较低。对他们的成纤维细胞的评估显示耗氧量增加和线粒体膜电位降低。外显子组分析揭示了 ATP5F1B 中的从头杂合变体，该变体编码线粒体 ATP 合酶的 β 亚基（也称为复合体 V）。在酵母中，影响同一区域的突变会放松质子动力和 ATP 合成之间的耦合，从而导致线粒体呼吸速率加快。突变等位基因在人类细胞系中的表达概括了这种表型。这些数据支持常染色体显性线粒体解偶联综合征伴代谢亢进。
We describe the case of identical twin boys who presented with low body weight despite excessive caloric intake. An evaluation of their fibroblasts showed elevated oxygen consumption and decreased mitochondrial membrane potential. Exome analysis revealed a de novo heterozygous variant in ATP5F1B, which encodes the β subunit of mitochondrial ATP synthase (also called complex V). In yeast, mutations affecting the same region loosen coupling between the proton motive force and ATP synthesis, resulting in high rates of mitochondrial respiration. Expression of the mutant allele in human cell lines recapitulates this phenotype. These data support an autosomal dominant mitochondrial uncoupling syndrome with hypermetabolism.