Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) – A Polish family with novel SACS mutations

Krygier, Magdalena; Konkel, Agnieszka; Schinwelski, Michał; Rydzanicz, Małgorzata; Walczak, Anna; Sildatke-Bauer, Magdalena; Płoski, Rafał; Sławek, Jarosław

doi:10.1016/j.pjnns.2017.08.003

Cited by 15 publications

(12 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our cohort of walkers, we noted that the proportion of people over 30 years who use a walking aid is higher than those in their twenties. People over 40 who maintain their walking ability do so mainly with a walking aid, an observation also reported in other studies (31,32). Results also show that ARSACS leads to a signi cant decrease in self-selected walking speed compared to the predictive values, mainly for walkers with a walking aid.…”

Section: Discussionsupporting

confidence: 83%

“…However, the prescription and the dosage are mainly to decrease the impact of neurogenic bladder and the presence of spasms in the lower limb. Only few studies have quanti ed spasticity in lower limb muscles using a standardized protocol for speed, angle of assessment, positioning and rating (1,16,32,33). Furthermore, the modi ed Ashworth scale is used worldwide in research and clinical follow-up but the interrater reliability is poor in ARSACS population (34).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Functional Mobility in Walking Adult Population With Ataxia of Charlevoix-Saguenay

Lessard

St-Gelais

Hébert

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: This study aimed to describe lower limbs impairments, balance and activity limitations related to indoor mobility in adult walkers with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Results: Twenty-five participants were recruited with a mean age of 32.2 (±10.4) years with 45.7 % using a walking aid. There is a significant difference between participants with and without a walking aid in terms of lower limbs coordination, balance and mobility. Although participants who walk without a walking aid perform better than the others and they are below predictive or reference values. Despite significant mobility limitations, only mild spasticity and passive range of motion limitations were observed. However, there is a significant difference between unaffected individuals and participants with ARSACS for lower limb muscle cocontraction. Conclusions: Results show a high level of lower limb impairments, balance and mobility limitation in adults’ participants with ARSACS that are still walking, including people not using a walking aid. One of the most original finding is the presence of excessive cocontraction and a relatively mild level of spasticity in the lower limbs muscles. Results of this study better circumscribes the impairments and activities that should be the focus of intervention including rehabilitation in ARSACS.

show abstract

Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Functional Mobility in Walking Adult Population With Ataxia of Charlevoix-Saguenay

Lessard

St-Gelais

Hébert

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…The mutation was missing in the healthy population, while unaffected siblings and the mother carried only one of these variants. Besides the classical ARSACS symptoms, affected patients presented cognitive or behavioral dysfunctions too [ 67 ]. A Russian case of the disease was discovered with atypically late onset of ARSACS and c.72276C>T (p.R2426X) mutation.…”

Section: Sacs Genetics and Mutationsmentioning

confidence: 99%

Genetics of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) and Role of Sacsin in Neurodegeneration

Bagaria

Bagyinszky

2022

IJMS

View full text Add to dashboard Cite

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disease that was originally discovered in the population from the Charlevoix-Saguenay-Lac-Saint-Jean (CSLSJ) region in Quebec. Although the disease progression of ARSACS may start in early childhood, cases with later onset have also been observed. Spasticity and ataxia could be common phenotypes, and retinal optic nerve hypermyelination is detected in the majority of patients. Other symptoms, such as pes cavus, ataxia and limb deformities, are also frequently observed in affected individuals. More than 200 mutations have been discovered in the SACS gene around the world. Besides French Canadians, SACS genetics have been extensively studied in Tunisia or Japan. Recently, emerging studies discovered SACS mutations in several other countries. SACS mutations could be associated with pathogenicity either in the homozygous or compound heterozygous stages. Sacsin has been confirmed to be involved in chaperon activities, controlling the microtubule balance or cell migration. Additionally, sacsin may also play a crucial role in regulating the mitochondrial functions. Through these mechanisms, it may share common mechanisms with other neurodegenerative diseases. Further studies are needed to define the exact functions of sacsin. This review introduces the genetic mutations discovered in the SACS gene and discusses its pathomechanisms and its possible involvement in other neurodegenerative diseases.

show abstract

“…Patients with macrodeletions that lead to loss of more than 3000 amino acids have similar phenotype to those that harbor single base insertion/deletions (indels) in the C-terminal end of the protein or that have missense substitutions (Bouhlal et al, 2011). Moreover, there are also reports of inter-or intrafamilial variability in patients with the same mutations (Bouhlal et al, 2011;Gagnon et al, 2018;Krygier et al, 2017). Some studies have been published trying to correlate the pathogenicity and/or the position of the SACS mutations with the age of onset or the clinical severity of the disease.…”

Section: Introductionmentioning

confidence: 99%

Sacsin cotranslational degradation causes autosomal recessive spastic ataxia of Charlevoix-Saguenay

Longo

Ritis

Miluzio

et al. 2021

Preprint

View full text Add to dashboard Cite

Autosomal recessive spastic ataxia of Charlevoix-Saguenay is caused by more than 200 different mutations in the SACS gene encoding sacsin, a huge multimodular protein of unknown function. ARSACS phenotypic spectrum is highly variable. Previous studies correlated the nature and position of SACS mutations with age of onset or disease severity, though the effects on protein stability were not considered. In this study, we explain mechanistically the lack of genotype-phenotype correlation in ARSACS, with important consequences for disease diagnosis and treatment. We found that sacsin is almost absent in ARSACS fibroblasts, regardless of the nature of the mutation. We did not detect sacsin in patients with truncating mutations, while we found it strikingly reduced or absent also in compound heterozygotes carrying diverse missense mutations. We excluded SACS mRNA decay, defective translation, or faster post-translational degradation as causes of protein reduction. Conversely, we demonstrated that nascent mutant sacsin protein undergoes preemptive cotranslational degradation, emerging as a novel cause of a human disease. Based on these findings, sacsin levels should be included in the diagnostic algorithm for ARSACS.

show abstract

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) – A Polish family with novel SACS mutations

Cited by 15 publications

References 9 publications

Functional Mobility in Walking Adult Population With Ataxia of Charlevoix-Saguenay

Functional Mobility in Walking Adult Population With Ataxia of Charlevoix-Saguenay

Genetics of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) and Role of Sacsin in Neurodegeneration

Sacsin cotranslational degradation causes autosomal recessive spastic ataxia of Charlevoix-Saguenay

Contact Info

Product

Resources

About