Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a progressive late-onset, neurological disease. Recently, a pentanucleotide expansion in intron 2 of RFC1 was identified as the genetic cause of CANVAS. We screened an Asian-Pacific cohort for CANVAS and identified a novel RFC1 repeat expansion motif, (ACAGG)_exp, in three affected individuals. This motif was associated with additional clinical features including fasciculations and elevated serum creatine kinase. These features have not previously been described in individuals with genetically-confirmed CANVAS. Haplotype analysis showed our patients shared the same core haplotype as previously published, supporting the possibility of a single origin of the RFC1 disease allele. We analysed data from >26 000 genetically diverse individuals in gnomAD to show enrichment of (ACAGG) in non-European populations.

中文翻译：

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两个亚太帆布家族中的新型 RFC1 重复基序 (ACAGG)

小脑性共济失调、神经病和前庭反射消失综合征 (CANVAS) 是一种进行性迟发性神经系统疾病。最近，RFC1内含子 2 中的五核苷酸扩增被确定为 CANVAS 的遗传原因。我们筛选了一个亚太地区的 CANVAS 队列，并在三个受影响的个体中确定了一个新的RFC1重复扩展基序 (ACAGG) _exp。该基序与其他临床特征相关，包括肌束颤动和血清肌酸激酶升高。这些特征以前没有在基因确认的 CANVAS 个体中被描述过。单倍型分析显示，我们的患者与之前发表的内容共享相同的核心单倍型，支持RFC1单一起源的可能性疾病等位基因。我们分析了来自 gnomAD 中超过 26 000 名遗传多样性个体的数据，以显示 (ACAGG) 在非欧洲人群中的富集。