Research Unit of Clinical Neuroscience, Neurology, University of Oulu, Oulu, Finland; MRC, Oulu University Hospital and University of Oulu, Oulu, Finland.
Research Unit of Clinical Neuroscience, Neurology, University of Oulu, Oulu, Finland; MRC, Oulu University Hospital and University of Oulu, Oulu, Finland; OUH Neurocenter, Neurology, Oulu University Hospital, FI-90029, Oulu, Finland.
Parkinsonism Relat Disord. 2022 Oct;103:98-101. doi: 10.1016/j.parkreldis.2022.08.034. Epub 2022 Sep 6.
The biallelic repeat expansion (AAGGG) in RFC1 causes cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS). Recently, cognitive impairment has been reported in patients with CANVAS and a broader neurodegenerative process associated with RFC1 has been suggested. Furthermore, rare cases of multiple system atrophy, Parkinson's disease, amyotrophic lateral sclerosis or CANVAS with features of dementia with Lewy bodies have been found.
We hypothesized that the biallelic (AAGGG) is associated with neurodegeneration manifested as cognitive symptoms and that atypical RFC1 disease may be found among patients with cognitive disorder.
Clinical data on nine patients with biallelic (AAGGG) were reviewed and 564 patients with Alzheimer's disease or frontotemporal dementia (FTD) were investigated for biallelic RFC1 (AAGGG).
Five patients with biallelic (AAGGG) were found with a cognitive impairment and in four of them the phenotype resembled FTD. However, biallelic (AAGGG) was not detected among patients with Alzheimer's disease or FTD.
Cognitive impairment is a feature in patients with the biallelic (AAGGG), but the pathogenic expansion seems to be rare in patients with dementia. Studies on patients with diverse phenotypes would be useful to further explore the involvement of RFC1 in neuronal degeneration and to identify atypical phenotypes, which should be taken into account in clinical practice.
RFC1 的双等位基因重复扩展（AAGGG）导致小脑共济失调、神经病和前庭反射消失综合征（CANVAS）。最近，CANVAS 患者报告了认知障碍，并且已经提出了与 RFC1 相关的更广泛的神经退行性过程。此外，还发现了少数多系统萎缩、帕金森病、肌萎缩侧索硬化症或具有路易体痴呆特征的 CANVAS 病例。
我们假设双等位基因（AAGGG）与以认知症状为表现的神经退行性变有关，并且在认知障碍患者中可能会发现不典型的 RFC1 疾病。
回顾了 9 名双等位基因（AAGGG）患者的临床数据，并对 564 名阿尔茨海默病或额颞叶痴呆（FTD）患者进行了双等位基因 RFC1（AAGGG）检测。
发现了 5 名具有双等位基因（AAGGG）的认知障碍患者，其中 4 名患者的表型类似于 FTD。然而，在阿尔茨海默病或 FTD 患者中未检测到双等位基因（AAGGG）。
认知障碍是双等位基因（AAGGG）患者的一个特征，但致病性扩展在痴呆患者中似乎很少见。对具有不同表型的患者进行研究将有助于进一步探讨 RFC1 在神经元退行性变中的作用，并识别不典型表型，这在临床实践中应予以考虑。
