Abstract：
BACKGROUND: Exome sequencing (ES) is a useful tool in diagnosing suspected mitochondrial disease but can miss pathogenic variants for several reasons. Additional testing, such as muscle biopsy or biochemical testing, can be helpful in exome-negative cases.
METHODS: We report a patient who presented with repeated episodes of lactic acidosis and failure to thrive.
RESULTS: ES and mitochondrial sequencing were initially negative but clinical suspicion for mitochondrial disease remained high. After muscle biopsy showed evidence of mitochondrial dysfunction, the ES was reanalyzed and revealed novel variants in AARS2.
CONCLUSIONS: This case demonstrates the importance of muscle biopsy and biochemical testing in evaluating patients with a high suspicion of mitochondrial disease, even in the genomics era. Closed-loop communication between molecular genetics laboratories and clinical geneticists is an important step to help establish diagnosis in unsolved cases.
METHODS: We report a patient who presented with repeated episodes of lactic acidosis and failure to thrive.
RESULTS: ES and mitochondrial sequencing were initially negative but clinical suspicion for mitochondrial disease remained high. After muscle biopsy showed evidence of mitochondrial dysfunction, the ES was reanalyzed and revealed novel variants in AARS2.
CONCLUSIONS: This case demonstrates the importance of muscle biopsy and biochemical testing in evaluating patients with a high suspicion of mitochondrial disease, even in the genomics era. Closed-loop communication between molecular genetics laboratories and clinical geneticists is an important step to help establish diagnosis in unsolved cases.
摘要：
背景：外显子组测序（ES）是诊断可疑线粒体疾病的有用工具，但由于多种原因可能会错过致病性变异。附加测试,如肌肉活检或生化检测，在外显子组阴性的情况下可能会有所帮助。
方法：我们报告了一例表现为乳酸性酸中毒反复发作且未能茁壮成长的患者。
结果：ES和线粒体测序最初呈阴性，但临床对线粒体疾病的怀疑仍然很高。肌肉活检后显示线粒体功能障碍的证据，对ES进行了重新分析,揭示了AARS2中的新变体.
结论：该病例证明了肌肉活检和生化检测在评估高度怀疑线粒体疾病患者中的重要性。即使在基因组学时代。分子遗传学实验室和临床遗传学家之间的闭环交流是帮助在未解决的病例中建立诊断的重要步骤。
方法：我们报告了一例表现为乳酸性酸中毒反复发作且未能茁壮成长的患者。
结果：ES和线粒体测序最初呈阴性，但临床对线粒体疾病的怀疑仍然很高。肌肉活检后显示线粒体功能障碍的证据，对ES进行了重新分析,揭示了AARS2中的新变体.
结论：该病例证明了肌肉活检和生化检测在评估高度怀疑线粒体疾病患者中的重要性。即使在基因组学时代。分子遗传学实验室和临床遗传学家之间的闭环交流是帮助在未解决的病例中建立诊断的重要步骤。
