Section of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado, Aurora, CO, USA.
Department of Radiology, University of Colorado, and Children's Hospital Colorado, Aurora, CO, USA.
Mitochondrion. 2020 Nov;55:8-13. doi: 10.1016/j.mito.2020.08.009. Epub 2020 Sep 12.
Diagnosing complex V deficiencies caused by new variants in mitochondrial DNA is challenging due to the rarity, phenotypic diversity, and limited functional assessments. We describe a child with the m.9032T > C variant in MT-ATP6 encoding p.(Leu169Pro), with primary presentation of microcephaly, ataxia, hearing loss, and lactic acidosis. Functional studies reveal abnormal fragment F of complex V on blue native gel electrophoresis. Respirometry showed excessively tight coupling through complex V depressing oxygen consumption upon ADP stimulation and an excessive increase following uncoupling, in the presence of upregulation of mitochondrial biogenesis. These data add evidence about pathogenicity and functional impact of this variant.
由于罕见性、表型多样性和有限的功能评估，诊断由线粒体 DNA 中新变体引起的复杂 V 缺乏症具有挑战性。我们描述了一名儿童，其 MT-ATP6 编码的 p.(Leu169Pro)中的 m.9032T > C 变体，主要表现为小头畸形、共济失调、听力损失和乳酸性酸中毒。功能研究显示蓝色非变性凝胶电泳上的复合物 V 异常片段 F。呼吸测定法显示，在存在线粒体生物发生上调的情况下，当 ADP 刺激时，复合物 V 抑制耗氧量，解偶联后复合物 V 抑制耗氧量过度增加，表明复合物 V 耦合过度。这些数据提供了关于该变体致病性和功能影响的证据。
