Novel SACS mutations identified by whole exome sequencing in a norwegian family with autosomal recessive spastic ataxia of Charlevoix-Saguenay

Charalampos Tzoulis; Stefan Johansson; Bjørn Ivar Haukanes; Helge Boman; Per Morten Knappskog; Laurence A Bindoff

doi:10.1371/journal.pone.0066145

Novel SACS mutations identified by whole exome sequencing in a norwegian family with autosomal recessive spastic ataxia of Charlevoix-Saguenay

PLoS One. 2013 Jun 13;8(6):e66145. doi: 10.1371/journal.pone.0066145. Print 2013.

Authors

Charalampos Tzoulis¹, Stefan Johansson, Bjørn Ivar Haukanes, Helge Boman, Per Morten Knappskog, Laurence A Bindoff

Affiliation

¹ Department of Neurology, Haukeland University Hospital, Bergen, Norway ; Department of Clinical Medicine, University of Bergen, Bergen, Norway.

Abstract

We employed whole exome sequencing to investigate three Norwegian siblings with an autosomal recessive spastic ataxia and epilepsy. All patients were compound heterozygous (c.13352T>C, p.Leu4451Pro; c.6890T>G, p.Leu2297Trp) for mutations in the SACS gene establishing the diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). The clinical features shown by our patients were typical of this disorder with the exception of epilepsy, which is a rare manifestation. This is the first report of ARSACS in Scandinavian patients and our findings expand the genetic and clinical spectrum of this rare disorder. Moreover, we show that exome sequencing is a powerful and cost-effective tool for the diagnosis of genetically heterogeneous disorders such as the hereditary ataxias.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Amino Acid Sequence
Brain / pathology
Exome
Family
Female
Genes, Recessive*
Heat-Shock Proteins / genetics*
Heterozygote
High-Throughput Nucleotide Sequencing
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Molecular Sequence Data
Muscle Spasticity / diagnosis
Muscle Spasticity / genetics*
Mutation*
Norway
Sequence Alignment
Spinocerebellar Ataxias / congenital*
Spinocerebellar Ataxias / diagnosis
Spinocerebellar Ataxias / genetics

Substances

Heat-Shock Proteins
SACS protein, human

Supplementary concepts

Spastic ataxia Charlevoix-Saguenay type

Grants and funding

This work was supported by grants from the Western Norway Health Trust, University of Bergen. Western Norway Regional Health Authority (Helse Vest). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.