Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodevelopmental disorder characterized by the association of spastic ataxia and sensorimotor neuropathy. Additional features include retinal changes and cognitive impairment. Today, next-generation sequencing (NGS) techniques are allowing the rapid identification of a growing number of missense variants, even in less typical forms of the disease, but the pathogenic significance of these changes is often difficult to establish on the basis of classic bioinformatics criteria and genotype/phenotype correlations. Herein, we describe two novel cases of missense mutations in SACS. The two individuals were identified during the genetic screening of a large cohort of patients with inherited ataxias. We discuss how protein studies and specialized ophthalmological investigations could represent useful pointers for the interpretation of genetic data. Combination of these tools with NGS for rapid genotyping might help to identify new true ARSACS cases.

中文翻译：

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在两个新的ARSACS病例中的临床和分子研究。

Charlevoix-Saguenay的常染色体隐性痉挛性共济失调（ARSACS）是一种早期发作的神经发育障碍，其特征为痉挛性共济失调和感觉运动神经病。其他功能包括视网膜改变和认知障碍。如今，下一代测序（NGS）技术可以快速识别越来越多的错义变体，即使是在疾病的典型形式中也是如此，但是这些变化的致病意义通常很难在经典生物信息学的基础上确定标准和基因型/表型的相关性。在此，我们描述了SACS中两个新的错义突变案例。在对一大批遗传性共济失调患者进行基因筛查期间确定了这两个人。我们讨论了蛋白质研究和专门的眼科研究如何代表遗传数据解释的有用指示。将这些工具与NGS结合使用以进行快速基因分型可能有助于识别新的真实ARSACS病例。