RFC1 repeat expansion in Japanese patients with late-onset cerebellar ataxia
RFC1 repeat expansion in Japanese patients with late-onset cerebellar ataxia
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DOI：
10.1038/s10038-020-0807-x
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发表时间：
2020-07-21
影响因子：
3.5
通讯作者：
Takiyama, Yoshihisa
中科院分区：
文献类型：
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作者：
Tsuchiya, Mai;Nan, Haitian;Takiyama, Yoshihisa
最近，复制因子C亚单位1(RFC1)基因内含子AAGGG重复序列的扩增被报道引起小脑性共济失调、神经病变、前庭反射综合征(Canvas)。在欧洲人中，晚期共济失调的散发性患者中有22%是扩张性的。我们对37例日本患者进行了基因分型，其中25例为家族性(常染色体隐性或不明遗传)，12例为散发性迟发性共济失调。我们在3名(12%)家族性患者和1名散发性患者(8.5%)中发现Rfc1基因内含子重复扩增。尽管我们的队列研究规模较小，但日本帆布患者的患病频率可能低于欧洲患者。此外，我们在1例患者中发现了双等位基因ACAGG重复扩增，表明ACAGG重复扩增可能导致画布。临床上，我们发现一名患者患有睡眠呼吸暂停综合征，这是以前没有报道过的。因此，这项研究可能会扩大帆布的临床和遗传谱。
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.