OBJECTIVE To present the postmortem neuropathologic report of a patient with a CHCHD10 mutation exhibiting an amyotrophic lateral sclerosis (ALS) clinical phenotype. METHODS A 54-year-old man without significant medical history or family history presented with arm weakness, slowly progressed over 19 years to meet the El Escorial criteria for clinically probable ALS with bulbar and respiratory involvement, and was found to have a CHCHD10 p.R15L mutation. Postmortem neuropathologic examination took place including immunohistochemical staining with CHCHD10, and double immunofluorescence combining CHCHD10 with TDP43 and neurofilament was performed and the results were compared with normal controls and sporadic ALS cases. RESULTS Postmortem examination of the CHCHD10 mutation carrier showed severe loss of hypoglossal and anterior horn motor neurons, mild corticospinal tract degeneration, and a relative lack of TDP43 immunopathology. CHCHD10 immunohistochemistry for the 3 controls and the 5 sporadic ALS cases showed strong neuronal cytoplasmic and axonal labeling, with the CHCHD10 mutation carrier also having numerous CHCHD10 aggregates within their anterior horns. These aggregates may be related to the CHCHD10 aggregates recently described to cause mitochondrial degeneration and disease in a tissue-selective toxic gain-of-function fashion in a CHCHD10 knock-in mouse model. The CHCHD10 aggregates did not colocalize with TDP43 and were predominantly extracellular on double immunofluorescence labeling with neurofilament. CONCLUSIONS The neuropathology of CHCHD10 mutated ALS includes predominantly lower motor neuron degeneration, absent TDP43 immunopathology, and aggregates of predominantly extracellular CHCHD10, which do not contain TDP43.

中文翻译：

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CHCHD10 突变的肌萎缩侧索硬化的神经病理学描述。

目的 呈现 CHCHD10 突变患者的尸检神经病理学报告，该突变表现出肌萎缩侧索硬化 (ALS) 临床表型。方法 一名没有明显病史或家族史的 54 岁男性出现手臂无力，在 19 年内缓慢进展，以符合 El Escorial 临床可能 ALS 伴延髓和呼吸系统受累的标准，并被发现患有 CHCHD10 p。 R15L 突变。进行死后神经病理学检查，包括用CHCHD10进行免疫组织化学染色，并进行CHCHD10与TDP43和神经丝结合的双重免疫荧光检查，并将结果与​​正常对照和散发性ALS病例进行比较。结果 CHCHD10 突变携带者的尸检显示舌下和前角运动神经元严重丧失，轻度皮质脊髓束变性，TDP43 免疫病理学相对缺乏。3 名对照和 5 名散发性 ALS 病例的 CHCHD10 免疫组织化学显示强烈的神经元细胞质和轴突标记，CHCHD10 突变载体在其前角内也有许多 CHCHD10 聚集体。这些聚集体可能与最近描述的 CHCHD10 聚集体有关，该聚集体在 CHCHD10 敲入小鼠模型中以组织选择性毒性功能获得方式引起线粒体变性和疾病。CHCHD10 聚集体不与 TDP43 共定位，并且在用神经丝进行双重免疫荧光标记时主​​要在细胞外。结论 CHCHD10 突变 ALS 的神经病理学主要包括下运动神经元变性，缺乏 TDP43 免疫病理学，