Recently, the expansion of an intronic AAGGG repeat in the replication factor C subunit 1 (RFC1) gene was reported to cause cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). In Europeans, the expansion accounted for 22% of sporadic patients with late-onset ataxia. We genotyped 37 Japanese patients comprising 25 familial (autosomal recessive or undecided transmission) and 12 sporadic ones with late-onset ataxia. We found intronic repeat expansions in RFC1 in three (12%) of the familial patients and one (8.5%) of the sporadic ones. Although our cohort study was small, the disease frequency in Japanese patients with CANVAS might be lower than that in European ones. In addition, we found biallelic ACAGG repeat expansion in one patient, indicating ACAGG repeat expansion might cause CANVAS. Clinically, we found one patient with sleep apnea syndrome, which has not been reported previously. Thus, this study might expand the clinical and genetic spectrum of CANVAS.

最近，据报道复制因子C亚基1（RFC1）基因中内含AAGGG重复序列的扩增引起小脑性共济失调，神经病，前庭反射乏力综合征（CANVAS）。在欧洲人中，扩展占散发性晚期共济失调患者的22％。我们对37例日本患者进行了基因分型，包括25例家族性（常染色体隐性或未确定的传播）和12例散发性晚期共济失调患者。我们在RFC1中发现了内含子重复扩展在三名（12％）家族患者和一名（8.5％）散发性患者中。尽管我们的队列研究很小，但日本CANVAS患者的发病率可能低于欧洲患者。此外，我们在一名患者中发现双等位基因ACAGG重复扩增，表明ACAGG重复扩增可能引起CANVAS。在临床上，我们发现了一名睡眠呼吸暂停综合症患者，该病先前未见报道。因此，本研究可能会扩大CANVAS的临床和遗传谱。