From the Departments of Neurology (Y.S.K., H.K., S.M.L., S.Y.M.) and Otolaryngology (Y.-H.C.), Ajou University School of Medicine, Suwon; Department of Laboratory Medicine (Y.-E.K.), Hanyang University College of Medicine, Seoul; Department of Neurology (H.J.K.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; Department of Neurology (N.-Y.J.), Pusan National University Yangsan Hospital, Research Institute for Convergence of Biomedical Science and Technology; and Department of Neurology (E.-J.K.), Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Busan, South Korea.
Neurology. 2023 Nov 14;101(20):e2046-e2050. doi: 10.1212/WNL.0000000000207832. Epub 2023 Aug 30.
Chromosome 9 open reading frame 72 () gene pathogenic variants have been typically associated with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), but recent studies suggest their involvement in other disorders. This report describes a family with an autosomal dominant pattern of inheritance of progressive verbal auditory agnosia due to GGGGCC repeat expansion in C9orf72. A 60-year-old right-handed male truck driver presented with slowly progressive poor speech perception for 8 years, which became most troublesome when receiving verbal orders over the phone. He had difficulty recognizing single-syllable spoken words beyond his hearing loss but had no problem understanding complex written language. He had a heterozygous pathogenic variant carrying 160 hexanucleotide repeats in the C9orf72 gene. His family history included his deceased mother with similar symptoms that had progressed over 30 years, as well as his older brother and youngest sister who experienced speech perception difficulty beginning in their early fifties. His asymptomatic younger brother had a heterozygous 2 repeat in the C9orf72 gene, while his symptomatic youngest sister had a heterozygous 159 repeat. The patient and his sister exhibited more pronounced cortical thinning in the frontotemporoparietal areas. The discrepancy observed between the distribution of atrophy and the presentation of symptoms in patients with C9orf72 pathogenic repeat expansion may be attributable to the slow progression of their clinical course over time. The variable symptom presentation of C9orf72 pathogenic repeat expansion highlights the importance of considering this pathogenic variant as a potential cause of autosomal dominant degenerative brain diseases beyond FTD and ALS.
9 号染色体开放阅读框 72()基因的致病变体通常与额颞叶痴呆 (FTD) 和肌萎缩性侧索硬化症 (ALS) 相关，但最近的研究表明它们与其他疾病有关。本报告描述了一个家族，其存在 C9orf72 中 GGGGCC 重复扩展导致的常染色体显性遗传性进行性言语听觉认知障碍。一位 60 岁的右利手男性卡车司机因进行性言语感知障碍就诊，该症状已经持续 8 年，在接听电话时的口头指令最为明显。他在听力损失的情况下很难识别单音节口语，但理解复杂的书面语言没有问题。他携带一个杂合致病性变体，C9orf72 基因中含有 160 个六核苷酸重复。他的家族史包括他患有类似症状的已故母亲，该症状已经进展超过 30 年，以及他的哥哥和妹妹，他们在五十多岁时开始出现言语感知困难。他无症状的弟弟在 C9orf72 基因中携带一个 2 个重复，而他有症状的妹妹携带一个 159 个重复。患者和他的妹妹在前颞顶枕区域表现出更明显的皮质变薄。在 C9orf72 致病重复扩展患者中观察到的萎缩分布与症状表现之间的差异可能归因于他们的临床病程随时间的缓慢进展。C9orf72 致病重复扩展的不同症状表现强调了将这种致病变体视为除 FTD 和 ALS 之外，潜在的常染色体显性退行性脑疾病的重要性。
