A novel homozygous SACS mutation identified by whole exome sequencing-genotype phenotype correlations of all published c
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A novel homozygous SACS mutation identified by whole exome sequencing-genotype phenotype correlations of all published cases Georgia Xiromerisiou 1 & Katerina Dadouli 2 & Chrysoula Marogianni 3 & Antonios Provatas 3 & Panagiotis Ntellas 4 & Dimitrios Rikos 3 & Pantelis Stathis 5 & Despina Georgouli 3 & Gedeon Loules 8 & Maria Zamanakou 8 & Georgios M. Hadjigeorgiou 6,7 Received: 14 August 2019 / Accepted: 26 September 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019
Abstract 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. Keywords Autosomal recessive spastic ataxia of Charlevoix-Saguenay . ARSACS . SACS gene . Spastic ataxia . Ataxia and polyneuropathy
Introduction Autosomal recessive spastic ataxia of Charlevoix-Saguenay, known as ARSACS, is characterized mainly by progressive cerebellar ataxia, spasticity, and sensorimotor peripheral neuropathy. Many other cases with atypical characteristics have been reported, such as intellectual disability, epileptic
seizures, hearing loss, and others. Originally, the first families have been described in the region of Charlevoix-Saguenay, in Quebec (Bouchard et al. 1978, 1979). Many other cases have been reported worldwide since then. ARSACS is caused by mutations in SACS gene which is located on chromosome 13q12.12. The gene was first described in 2000 (Richter et al. 1999; Engert et al. 2000). The
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12031-019-01410-z) contains supplementary material, which is available to authorized users. * Georgia Xiromerisiou [email protected] 1
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Department of Medical Oncology, University Hospital o
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