Clinical and Genetic Variability Among Bulgarian Patients with Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay

Overview

Journal Mol Genet Genomic Med

Specialty Genetics

Date 2024 Jul 24

PMID 39044368

Authors

Teodora Chamova

Neviana Ivanova

Sylvia Cherninkova

Maya Koleva

Dora Zlatareva

Veneta Bojinova

Kalina Mihova

Martin Georgiev

Dilyan Ferdinandov

Stoyan Bichev

Radka Kaneva

Vanio Mitev

Albena Jordanova

Ivailo Tournev

Affiliations

Soon will be listed here.

Abstract

Background: Autosomal recessive spastic ataxia ofCharlevoix-Saguenay (ARSACS) is a rare neurodegenerative disorder characterizedby early-onset cerebellar ataxia, peripheral sensorimotor neuropathy, and lowerlimb spasticity. We present clinical andgenetic data of the first Bulgarian patients diagnosed with ARSACS by wholeexome sequencing (WES).

Methods: Variant filtering was performed usinglocally established pipeline and the selected variants were analysed by Sangersequencing. All patients underwent clinical examination and testingincluding the standard rating scales for spastic paraplegia and ataxia.

Results: Five different SACS gene variants, three of which novel, have been identified inpatients from three different ethnic groups. In addition to the classicalclinical triad, brain MRI revealed cerebellar atrophy, linear pontineT2-hypointensities, and hyperintense rim lateral tothalamus combined with retinal nerve fiber layer thickening on opticcoherence tomography (OCT).

Conclusion: We expand the mutation, geographic, and phenotypic spectrum of ARSACS, adding Bulgaria to the world map of the disease, and drawing attention to the fact that it is still misdiagnosed. We demonstrated that brain MRI and OCT are necessary clinical tests for ARSACS diagnosis, even if one of the cardinal clinical features is lacking.

Citing Articles

Clinical and genetic variability among Bulgarian patients with autosomal recessive spastic ataxia of Charlevoix-Saguenay.

Chamova T, Ivanova N, Cherninkova S, Koleva M, Zlatareva D, Bojinova V Mol Genet Genomic Med. 2024; 12(7):e2483.

PMID: 39044368 PMC: 11266115. DOI: 10.1002/mgg3.2483.

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