The ataxias comprise diseases of both genetic and nongenetic origin with extreme clinical and genetic heterogeneity. They may present as a pure cerebellar form or as part of a more complex neurologic syndrome. Progressive, neurodegenerative sporadic adult-onset ataxias (SAOAs) without a known cause have a prevalence rate of 2.2–12.4 per 100,000. In several ataxia cohorts, repetitive genetic screening using high-coverage ataxia-specific gene panels in combination with next-generation sequencing (NGS) failed to identify a causative gene in 50%–90% of SAOAs.^1–3 Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS), first described by Brownstein et al.,⁴ is a slowly progressive neurodegenerative disorder with adult onset, affecting the cerebellum, sensory neurons, and the vestibular system. CANVAS is usually sporadic, but occasionally occurs in siblings. Two research groups recently identified large biallelic intronic AAGGG expansions in replication factor C subunit 1 (RFC1) resulting in CANVAS, an adult-onset neurodegenerative ataxia.^5–7 RFC1 normally loads proliferating cell nuclear antigen onto DNA and activates DNA polymerases and to promote the coordinated synthesis of both strands during replication or after DNA damage.⁸

共济失调包括具有极端临床和遗传异质性的遗传和非遗传来源的疾病。它们可能以纯小脑形式出现，也可能是更复杂的神经系统综合症的一部分。进行性神经退行性散发性成人共济失调（SAOA）无已知原因，患病率为2.2-12.4 / 10万。在一些共济失调人群中，使用高覆盖共济失调特异性基因组结合下一代测序（NGS）进行的重复遗传筛选未能在50％至90％的SAOA中鉴定出致病基因。^1-3小脑共济失调，神经病，前庭反射乏力综合征（CANVAS），最早由Brownstein等人[ ^4]描述是一种缓慢进展的神经退行性疾病，成人发作，影响小脑，感觉神经元和前庭系统。CANVAS通常是零星的，但偶尔会发生在兄弟姐妹中。最近有两个研究小组确定了复制因子C亚基1（RFC1）中较大的双等位基因内含子AAGGG扩增，导致成人成年神经退行性共济失调CANVAS。^5-7 RFC1通常将增殖的细胞核抗原加载到DNA上并激活DNA聚合酶，并在复制过程中或DNA损伤后促进两条链的协调合成。⁸