A Novel Homozygous SACS Mutation Identified by Whole Exome Sequencing-genotype Phenotype Correlations of All Published Cases

Overview

Journal J Mol Neurosci

Specialties Molecular Biology
Neurology

Date 2019 Nov 9

PMID 31701440

Citations 16

Authors

Georgia Xiromerisiou

Katerina Dadouli

Chrysoula Marogianni

Antonios Provatas

Panagiotis Ntellas

Dimitrios Rikos

Pantelis Stathis

Despina Georgouli

Gedeon Loules

Maria Zamanakou

Georgios M Hadjigeorgiou

Affiliations

Soon will be listed here.

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.

Citing Articles

Whole Blood DNA Methylation Analysis Reveals Epigenetic Changes Associated with ARSACS.

De Riso G, Naef V, Damiani D, Doccini S, Santorelli F, Galatolo D Cerebellum. 2025; 24(2):36.

PMID: 39853590 DOI: 10.1007/s12311-025-01791-5.

ARSACS: Clinical Features, Pathophysiology and iPS-Derived Models.

Salem I, Blais M, Zuluaga-Sanchez V, Rouleau L, Becker E, Dupre N Cerebellum. 2025; 24(1):24.

PMID: 39753868 DOI: 10.1007/s12311-024-01777-9.

Longitudinal Imaging Biomarkers Correlate with Progressive Motor Deficit in the Mouse Model of Charlevoix-Saguenay Ataxia.

Gigliucci V, Huang S, Boschetti G, Scaravilli A, Castoldi V, Podini P Ann Neurol. 2024; 97(3):425-434.

PMID: 39641374 PMC: 11831876. DOI: 10.1002/ana.27146.

Reduction of sacsin levels in peripheral blood mononuclear cells as a diagnostic tool for spastic ataxia of Charlevoix-Saguenay.

De Ritis D, Ferre L, De Winter J, Tremblay-Desbiens C, Blais M, Bassi M Brain Commun. 2024; 6(4):fcae243.

PMID: 39091421 PMC: 11291951. DOI: 10.1093/braincomms/fcae243.

An overview of early-onset cerebellar ataxia: a practical guideline.

Hosseinpour S, Bemanalizadeh M, Mohammadi P, Ashrafi M, Heidari M Acta Neurol Belg. 2024; 124(6):1791-1804.

PMID: 38951452 DOI: 10.1007/s13760-024-02595-w.

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