Molecular Medicine, IRCCS Fondazione Stella Maris, via dei Giacinti 2 Calambrone, 56128, Pisa, Italy.
Pediatric Ophthalmology Unit, Meyer Children's Hospital, University of Florence, Florence, Italy.
Neurogenetics. 2019 Mar;20(1):45-49. doi: 10.1007/s10048-019-00564-7. Epub 2019 Jan 24.
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.
常染色体隐性痉挛性共济失调型小脑性共济失调（ARCSACS）是一种早发性神经发育障碍，其特征是痉挛性共济失调和感觉运动神经病的合并。其他特征包括视网膜改变和认知障碍。如今，下一代测序（NGS）技术使得越来越多的错义变体的快速鉴定成为可能，即使在疾病的不太典型形式中也是如此，但这些变化的致病意义通常很难根据经典的生物信息学标准和基因型/表型相关性来确定。在此，我们描述了 SACS 中的两个新的错义突变病例。这两个人是在遗传性共济失调患者的大型队列的遗传筛查中发现的。我们讨论了蛋白质研究和专门的眼科检查如何为遗传数据分析提供有用的线索。将这些工具与 NGS 相结合进行快速基因分型可能有助于识别新的真正 ARCSACS 病例。
