biostudies-literatureUnknown97(23)Longo F<h4>Background and objectives</h4>Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is caused by variations in <i>SACS</i> gene encoding sacsin, a huge multimodular protein of unknown function. More than 200 <i>SACS</i> variations have been described worldwide to date. Because ARSACS presents phenotypic variability, previous empirical studies attempted to correlate the nature and position of <i>SACS</i> variations with the age at onset or with disease severity, although not considering the effect of the various variations on protein stability. In this work, we studied genotype-phenotype correlation in ARSACS at a functional level.<h4>Methods</h4>We analyzed a large set of skin fibroblasts derived from patients with ARSACS, including both new and already published cases, caNeurologye2315-e2327https://www.ebi.ac.uk/biostudies/studies/S-EPMC8665432biostudies-literatureAssessment of Sacsin Turnover in Patients With ARSACS: Implications for Molecular Diagnosis and Pathogenesis.PMC8665432Fraticelli DSantorelli FMBaets JScarlato MLongo FDe Ritis DMiluzio ABiffo SMaltecca FfalseAssessment of Sacsin Turnover in Patients With ARSACS: Implications for Molecular Diagnosis and Pathogenesis.<h4>Background and objectives</h4>Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is caused by variations in <i>SACS</i> gene encoding sacsin, a huge multimodular protein of unknown function. More than 200 <i>SACS</i> variations have been described worldwide to date. Because ARSACS presents phenotypic variability, previous empirical studies attempted to correlate the nature and position of <i>SACS</i> variations with the age at onset or with disease severity, although not considering the effect of the various variations on protein stability. In this work, we studied genotype-phenotype correlation in ARSACS at a functional level.<h4>Methods</h4>We analyzed a large set of skin fibroblasts derived from patients with ARSACS, including both new and already published cases, ca2021-01-01T00:00:00Z2021 Dec2025-04-04T13:12:44.149Z2022-02-11T14:02:45.518ZS-EPMC86654323464987410.1212/WNL.0000000000012962