Davies Kayli, Szmulewicz David J, Corben Louise A, Delatycki Martin, Lockhart Paul J
Bruce Lefroy Centre for Genetic Health Research (K.D., L.A.C., M.D., P.J.L.), Murdoch Children's Research Institute; Department of Paediatrics (K.D., L.A.C., M.D., P.J.L.), University of Melbourne, Parkville; Balance Disorders & Ataxia Service (D.S.), Royal Victorian Eye & Ear Hospital, East Melbourne; The Florey Institute of Neuroscience and Mental Health (D.S.), Parkville; and Victorian Clinical Genetics Services (M.D.), Melbourne, Australia.
Neurol Genet. 2022 Aug 29;8(5):e200016. doi: 10.1212/NXG.0000000000200016. eCollection 2022 Oct.
In 2019, a biallelic pentanucleotide repeat expansion in the gene encoding replication factor C subunit 1 () was reported as a cause of cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS). In addition, biallelic expansions were shown to account for up to 22% of cases with late-onset ataxia. Since this discovery, the phenotypic spectrum reported to be associated with expansions has extended beyond the initial conditions to include pure cerebellar ataxia, isolated somatosensory impairment, combinations of the 2, and parkinsonism, leading to a potentially broad differential diagnosis. Genetic studies suggest expansions may be the most common genetic cause of ataxia and are likely underdiagnosed. This review summarizes the current molecular and clinical knowledge of -related disease, with a focus on the evaluation of recent phenotype associations and highlighting the current challenges in clinical pathways to diagnosis and molecular testing.
2019年，有报道称编码复制因子C亚基1（）的基因中双等位五核苷酸重复扩增是导致伴有神经病变和前庭反射消失综合征（CANVAS）的小脑共济失调的一个病因。此外，双等位基因扩增在晚发性共济失调病例中所占比例高达22%。自这一发现以来，据报道与扩增相关的表型谱已超出最初的病症范围，包括单纯性小脑共济失调、孤立性躯体感觉障碍、两者的组合以及帕金森症，从而导致潜在的广泛鉴别诊断。遗传学研究表明，扩增可能是共济失调最常见的遗传病因，很可能未得到充分诊断。本综述总结了目前与相关疾病的分子和临床知识，重点评估了近期的表型关联，并强调了临床诊断途径和分子检测方面当前面临的挑战。
