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 F1 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.

中文翻译：

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MT-ATP6 编码 p.(Leu169Pro) 中的线粒体 DNA 变异 m.9032T>C 导致复杂的线粒体神经综合征

由于线粒体 DNA 的稀有性、表型多样性和有限的功能评估，诊断由线粒体 DNA 中的新变异引起的复杂 V 缺陷具有挑战性。我们描述了一个在 MT-ATP6 编码 p.(Leu169Pro) 中具有 m.9032T>C 变体的儿童，主要表现为小头畸形、共济失调、听力损失和乳酸性酸中毒。功能研究揭示了蓝色天然凝胶电泳上复合物 V 的异常片段 F1。在线粒体生物发生上调的情况下，呼吸测量显示通过复合 V 抑制 ADP 刺激时的氧消耗和解偶联后的过度增加而过度紧密耦合。这些数据增加了关于该变异的致病性和功能影响的证据。