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首页> 外文期刊>Neuropathology: official journal of the Japanese Society of Neuropathology >Clinicopathologic features of autosomal recessive amyotrophic lateral sclerosis associated with optineurin mutation
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Clinicopathologic features of autosomal recessive amyotrophic lateral sclerosis associated with optineurin mutation

机译：常染色体隐性肌萎缩性侧索硬化伴有optineurin突变的临床病理特征

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We performed clinicopathological analyses of two amyotrophic lateral sclerosis (ALS) patients with homozygous Q398Xoptineurin (OPTN) mutation. Clinically, both patients presented signs of upper and lower motor neuron degeneration, but only Patient 1 showed gradual frontal dysfunction and extrapyramidal signs, and temporal lobe and motor cortex atrophy. Neuropathological examination of Patient 1 revealed extensive cortical and spinal motor neuron degeneration and widespread degeneration of the basal ganglia. Bilateral corticospinal tracts exhibited degeneration. Loss of spinal anterior horn cells (AHCs) and gliosis were observed, whereas posterior columns, Clarke's columns, intermediate lateral columns, and the Onuf's nucleus were spared. In the brainstem, moderate neuronal loss and gliosis were noted in the hypoglossal and facial motor nuclei. No Bunina bodies were found in the surviving spinal and brainstem motor neurons. Transactivation response (TAR) DNA-binding protein 43 (TDP-43)-positive neuronal and glial cytoplasmic inclusions were observed throughout the central nervous system. The Golgi apparatus in motor neurons of the brainstem and spinal cord was often fragmented. Immunoreactivity for OPTN was not observed in the brain and spinal cord, consistent with nonsense-mediated mRNA decay of OPTN. The TDP-43 pathology of Q398X was similar to that of an autosomal dominant E478G mutation. This result suggests that the loss-of-function, but not the proteinopathy itself, of OPTN results in TDP-43 deposits in neuronal and glial cytoplasm and Golgi apparatus fragmentation, leading to multisystem neurodegeneration.
机译：我们对两名纯合Q398Xoptineurin（OPTN）突变的肌萎缩性侧索硬化（ALS）患者进行了临床病理分析。临床上，两名患者均表现出上下运动神经元变性的体征，但只有患者1表现出逐渐的额叶功能障碍和锥体外系体征，以及颞叶和运动皮质萎缩。患者1的神经病理学检查显示皮质和脊髓运动神经元广泛变性和基底神经节广泛变性。双侧皮质脊髓束表现出变性。观察到脊髓前角细胞（AHC）丢失和神经胶质增生，而后柱，克拉克柱，中间外侧柱和Onuf核则被保留。在脑干中，在舌下和面部运动核中发现了中度神经元丢失和神经胶质增生。在幸存的脊柱和脑干运动神经元中未发现布尼纳尸体。在整个中枢神经系统中观察到反式激活应答（TAR）DNA结合蛋白43（TDP-43）阳性的神经元和神经胶质细胞质包涵体。脑干和脊髓运动神经元中的高尔基体经常碎裂。在大脑和脊髓中未观察到OPTN的免疫反应性，这与OPTN的无意义介导的mRNA衰变一致。 Q398X的TDP-43病理与常染色体显性E478G突变相似。该结果表明，OPTN的功能丧失而不是蛋白病变本身，导致神经元和神经胶质细胞质中的TDP-43沉积以及高尔基体碎裂，从而导致多系统神经变性。

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