A Novel Exon Duplication in the SACS Gene in Charlevoix-Saguenay Ataxia and a Summary of Polish Cases

Mutations in the <i>SACS</i> gene are associated with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), a clinically and genetically heterogeneous neurodegenerative disorder. ARSACS typically manifests as slowly progressive ataxia with spasticity and sensorimotor neuropathy. Nevertheless, an array of additional features may also be observed, including hearing impairment, epileptic seizures, and even the absence of spasticity. Reports of <i>SACS</i> mutations in Polish patients are rare. Here we report a compound heterozygous pathogenic variants in the <i>SACS</i> gene, a novel duplication of exon 6, and a frameshift deletion c.12923_12927del 12921_12925del p.(Lys4308SerfsTer21) in a Polish patient presenting with progressive ataxia, spasticity, and peripheral neuropathy. This is the first case with a rearrangement of a complete single exon of the <i>SACS</i> gene. We also review six previously described Polish individuals with <i>SACS</i> variants, noting that all presented with cerebellar ataxic gait and cerebellar atrophy on brain MRI scans. Across these cases, nine rare pathogenic <i>SACS</i> variants were identified. This study adds to the ARSACS-associated mutation spectrum, provides further insights into genotype-phenotype correlations, and highlights the importance of testing for structural variants.