Department of Bionano Technology, Gachon University, Seongnam 13120, Korea.
Department of Industrial and Environmental Engineering, Graduate School of Environment, Gachon University, Seongnam 13120, Korea.
Int J Mol Sci. 2022 Jan 4;23(1):552. doi: 10.3390/ijms23010552.
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disease that was originally discovered in the population from the Charlevoix-Saguenay-Lac-Saint-Jean (CSLSJ) region in Quebec. Although the disease progression of ARSACS may start in early childhood, cases with later onset have also been observed. Spasticity and ataxia could be common phenotypes, and retinal optic nerve hypermyelination is detected in the majority of patients. Other symptoms, such as pes cavus, ataxia and limb deformities, are also frequently observed in affected individuals. More than 200 mutations have been discovered in the gene around the world. Besides French Canadians, genetics have been extensively studied in Tunisia or Japan. Recently, emerging studies discovered mutations in several other countries. mutations could be associated with pathogenicity either in the homozygous or compound heterozygous stages. Sacsin has been confirmed to be involved in chaperon activities, controlling the microtubule balance or cell migration. Additionally, sacsin may also play a crucial role in regulating the mitochondrial functions. Through these mechanisms, it may share common mechanisms with other neurodegenerative diseases. Further studies are needed to define the exact functions of sacsin. This review introduces the genetic mutations discovered in the gene and discusses its pathomechanisms and its possible involvement in other neurodegenerative diseases.
常染色体隐性痉挛性共济失调型脑白质营养不良（ARSACS）是一种早发性神经退行性疾病，最初在魁北克的沙勒瓦-圣让湖-圣安娜地区（CSLSJ）人群中发现。尽管 ARSACS 的疾病进展可能始于儿童早期，但也观察到了发病较晚的病例。痉挛和共济失调可能是常见的表型，大多数患者都存在视网膜视神经过度髓鞘化。在受影响的个体中，还经常观察到其他症状，如高弓足、共济失调和肢体畸形。在全球范围内已经发现了 基因的 200 多个突变。除了法裔加拿大人外，突尼斯或日本也对其遗传学进行了广泛研究。最近，新兴研究在其他几个国家发现了 突变。无论是在纯合子还是复合杂合子阶段， 突变都可能与致病性有关。Sacsin 已被证实参与伴侣活性，控制微管平衡或细胞迁移。此外，sacsin 还可能在调节线粒体功能方面发挥关键作用。通过这些机制，它可能与其他神经退行性疾病共享共同的机制。需要进一步研究来确定 sacsin 的确切功能。这篇综述介绍了在 基因中发现的遗传突变，并讨论了其发病机制及其在其他神经退行性疾病中的可能参与。
