scholarly journals Development of Nanostructured Lipid Carriers for the Delivery of Idebenone in Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay

ACS Omega ◽  
2020 ◽  
Vol 5 (21) ◽  
pp. 12451-12466 ◽  
Author(s):  
Chiara Martinelli ◽  
Matteo Battaglini ◽  
Carlotta Pucci ◽  
Sara Gioi ◽  
Chiara Caracci ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Nanostructured Lipid Carriers ◽  
Spastic Ataxia

scholarly journals Novel compound heterozygous mutation in SACS gene leads to a milder autosomal recessive spastic ataxia of Charlevoix‐Saguenay, ARSACS , in a Finnish family

2016 ◽  
Vol 4 (12) ◽  
pp. 1151-1156 ◽  
Author(s):  
Johanna Palmio ◽  
Mikko Kärppä ◽  
Peter Baumann ◽  
Sini Penttilä ◽  
Jukka Moilanen ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Spastic Ataxia

scholarly journals Biochemical Characterization of the GBA2 c.1780G>C Missense Mutation in Lymphoblastoid Cells from Patients with Spastic Ataxia

2018 ◽  
Vol 19 (10) ◽  
pp. 3099 ◽  
Author(s):  
Anna Malekkou ◽  
Maura Samarani ◽  
Anthi Drousiotou ◽  
Christina Votsi ◽  
Sandro Sonnino ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Autosomal Recessive ◽  
Biochemical Characterization ◽  
Fold Increase ◽  
Loss Of Function ◽  
Spastic Paraplegia ◽  
Spastic Ataxia ◽  
Autosomal Recessive Cerebellar Ataxia ◽  
Compensatory Effect

The GBA2 gene encodes the non-lysosomal glucosylceramidase (NLGase), an enzyme that catalyzes the conversion of glucosylceramide (GlcCer) to ceramide and glucose. Mutations in GBA2 have been associated with the development of neurological disorders such as autosomal recessive cerebellar ataxia, hereditary spastic paraplegia, and Marinesco-Sjogren-Like Syndrome. Our group has previously identified the GBA2 c.1780G>C [p.Asp594His] missense mutation, in a Cypriot consanguineous family with spastic ataxia. In this study, we carried out a biochemical characterization of lymphoblastoid cell lines (LCLs) derived from three patients of this family. We found that the mutation strongly reduce NLGase activity both intracellularly and at the plasma membrane level. Additionally, we observed a two-fold increase of GlcCer content in LCLs derived from patients compared to controls, with the C16 lipid being the most abundant GlcCer species. Moreover, we showed that there is an apparent compensatory effect between NLGase and the lysosomal glucosylceramidase (GCase), since we found that the activity of GCase was three-fold higher in LCLs derived from patients compared to controls. We conclude that the c.1780G>C mutation results in NLGase loss of function with abolishment of the enzymatic activity and accumulation of GlcCer accompanied by a compensatory increase in GCase.

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

2022 ◽  
Vol 23 (1) ◽  
pp. 552
Author(s):  
Jaya Bagaria ◽  
Eva Bagyinszky ◽  
Seong Soo A. An
Keyword(s):  
Neurodegenerative Diseases ◽  
Autosomal Recessive ◽  
Genetic Mutations ◽  
Compound Heterozygous ◽  
French Canadians ◽  
Pes Cavus ◽  
Spastic Ataxia ◽  
Mitochondrial Functions ◽  
Limb Deformities

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.

Private SACS mutations in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) families from Turkey

Neurogenetics ◽  
2004 ◽  
Vol 5 (3) ◽  
pp. 165-170 ◽  
Author(s):  
Andrea M. Richter ◽  
Riza Koksal Ozgul ◽  
Virginie C. Poisson ◽  
Haluk Topaloglu
Keyword(s):  
Autosomal Recessive ◽  
Spastic Ataxia

Retinal Imaging in Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay

2011 ◽  
Vol 35 (4) ◽  
pp. 197-201 ◽  
Author(s):  
Suran Nethisinghe ◽  
Lisa Clayton ◽  
Sascha Vermeer ◽  
J. Paul Chapple ◽  
Mary Reilly ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Retinal Imaging ◽  
Spastic Ataxia
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