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Abstract：
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a complex genetic architecture, showing monogenic, oligogenic, and polygenic inheritance. In this study, we describe the case of a 71 years-old man diagnosed with ALS with atypical clinical features consisting in progressive ocular ptosis and sensorineural deafness. Genetic analyses revealed two heterozygous variants, in the SOD1 (OMIM*147450) and the TBK1 (OMIM*604834) genes respectively, and furthermore mitochondrial DNA (mtDNA) sequencing identified the homoplasmic m.14484T>C variant usually associated with Leber\'s Hereditary Optic Neuropathy (LHON). We discuss how all these variants may synergically impinge on mitochondrial function, possibly contributing to the pathogenic mechanisms which might ultimately lead to the neurodegenerative process, shaping the clinical ALS phenotype enriched by adjunctive clinical features.
摘要：
肌萎缩侧索硬化症（ALS）是一种具有复杂遗传结构的神经退行性疾病，显示单基因，寡基因,和多基因遗传。在这项研究中,我们描述了一例71岁的男性患者,该患者诊断为ALS,其临床特征不典型,表现为进行性眼下垂和感音神经性耳聋.遗传分析揭示了两个杂合变异，在SOD1(OMIM*147450)和TBK1(OMIM*604834)基因中,此外，线粒体DNA（mtDNA）测序确定了通常与Leber遗传性视神经病变（LHON）相关的同质m.14484T>C变体。我们讨论了所有这些变体如何协同影响线粒体功能，可能有助于最终导致神经退行性过程的致病机制，塑造由辅助临床特征丰富的临床ALS表型。
