A novel homozygous SACS mutation identified by whole exome sequencing-genotype phenotype correlations of all published cases
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ARSACS is an autosomal recessive disorder characterized by ataxia, spasticity, and polyneuropathy. A plethora of worldwide distributed mutations have been described so far. Here, we report two brothers, born to non-consanguineous parents, presenting with cerebellar ataxia and peripheral neuropathy. Whole-exome sequencing revealed the presence of a novel homozygous variant in the SACS gene. The variant was confirmed by Sanger sequencing and found at heterozygous state in both parents. This is the first reported mutation in this gene, in Greek population. This case report further highlights the growing trend of identifying genetic diseases previously restricted to single, ethnically isolated regions in many different ethnic groups worldwide. Additionally, we performed a systematic review of all published cases with SACs mutations. ARSACS seems to be an important cause of ataxia and many different types of mutations have been identified, mainly located in exon 10. We evaluated the mutation pathogenicity in all previously reported cases to investigate possible phenotype-genotype correlations. We managed to find a correlation between the pathogenicity of mutations, severity of the phenotype, and age of onset of ARSACS. Greater mutation numbers in different populations will be important and mutation-specific functional studies will be essential to identify the pathogenicity of the various ARSACS variants.
KeywordsAutosomal recessive spastic ataxia of Charlevoix-Saguenay ARSACS SACS gene Spastic ataxia Ataxia and polyneuropathy
We are grateful to patients and their family for contributing to this study.
Compliance with Ethical Standards
Written informed consent for participation was obtained from patients and their guardians according to the Declaration of Helsinki and protocols were approved by the institutional review boards of the the Ethics Committee of the University Hospital of Larissa.
Conflict of Interest
The authors declare that they have no conflict of interest.
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