Advanced search
1 file | 728.34 KB

Mutations in SACS cause atypical and late-onset forms of ARSACS

(2010) NEUROLOGY. 75(13). p.1181-1188
Author
Organization
Abstract
Background : Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a complex neurodegenerative disorder caused by mutations in SACS. The phenotype consists of a childhood-onset triad of cerebellar ataxia, peripheral neuropathy, and pyramidal tract signs. Objective : To provide more insight into the prevalence of SACS mutations and the variability of the associated phenotype. Methods : Mutation screening of SACS by direct sequencing and multiplex amplicon quantification for detection of intragenic copy number variations in a cohort of 85 index patients with phenotypes suggestive for ARSACS. Additional short tandem repeat (STR) marker analysis was performed for haplotype sharing. Results : In 11 families, 18 new SACS mutations were found (12.9% of total cohort). Five patients displayed onset ages in adulthood, a feature not known to be associated with ARSACS. The remaining index patients displayed a classic early onset phenotype. Initial phenotypic presentation was atypical in several patients, obscuring the clinical diagnosis. A founder mutation in SACS was identified in 3 Belgian families. In one isolated patient, an intragenic SACS deletion of exons 3-5 was detected. Partial SACS deletions were not previously described. Conclusions : In this study, we enlarge the ARSACS phenotype and the underlying genetic spectrum of SACS mutations. Patients with ARSACS are more common than previously known and risk underdiagnosis due to late onset age and unusual presentation.
Keywords
CHARLEVOIX-SAGUENAY, RECESSIVE SPASTIC ATAXIA, CEREBELLAR-ATAXIA, GENE, PHENOTYPE, DELETION, FAMILY

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 728.34 KB

Citation

Please use this url to cite or link to this publication:

Chicago
Baets, J, T Deconinck, K Smets, D Goossens, P Van Den Bergh, K Dahan, E Schmedding, et al. 2010. “Mutations in SACS Cause Atypical and Late-onset Forms of ARSACS.” Neurology 75 (13): 1181–1188.
APA
Baets, J, Deconinck, T., Smets, K., Goossens, D., Van Den Bergh, P., Dahan, K., Schmedding, E., et al. (2010). Mutations in SACS cause atypical and late-onset forms of ARSACS. NEUROLOGY, 75(13), 1181–1188.
Vancouver
1.
Baets J, Deconinck T, Smets K, Goossens D, Van Den Bergh P, Dahan K, et al. Mutations in SACS cause atypical and late-onset forms of ARSACS. NEUROLOGY. 2010;75(13):1181–8.
MLA
Baets, J, T Deconinck, K Smets, et al. “Mutations in SACS Cause Atypical and Late-onset Forms of ARSACS.” NEUROLOGY 75.13 (2010): 1181–1188. Print.
@article{1113027,
  abstract     = {Background : Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a complex neurodegenerative disorder caused by mutations in SACS. The phenotype consists of a childhood-onset triad of cerebellar ataxia, peripheral neuropathy, and pyramidal tract signs.
Objective : To provide more insight into the prevalence of SACS mutations and the variability of the associated phenotype.
Methods : Mutation screening of SACS by direct sequencing and multiplex amplicon quantification for detection of intragenic copy number variations in a cohort of 85 index patients with phenotypes suggestive for ARSACS. Additional short tandem repeat (STR) marker analysis was performed for haplotype sharing.
Results : In 11 families, 18 new SACS mutations were found (12.9\% of total cohort). Five patients displayed onset ages in adulthood, a feature not known to be associated with ARSACS. The remaining index patients displayed a classic early onset phenotype. Initial phenotypic presentation was atypical in several patients, obscuring the clinical diagnosis. A founder mutation in SACS was identified in 3 Belgian families. In one isolated patient, an intragenic SACS deletion of exons 3-5 was detected. Partial SACS deletions were not previously described.
Conclusions : In this study, we enlarge the ARSACS phenotype and the underlying genetic spectrum of SACS mutations. Patients with ARSACS are more common than previously known and risk underdiagnosis due to late onset age and unusual presentation.},
  author       = {Baets, J and Deconinck, T and Smets, K and Goossens, D and Van Den Bergh, P and Dahan, K and Schmedding, E and Santens, Patrick and Rasic, Milic V and Van Damme, P and Robberecht, W and De Meirleir, L and Michielsens, B and Del-Favero, J and Jordanova, A and De Jonghe, P},
  issn         = {0028-3878},
  journal      = {NEUROLOGY},
  keyword      = {CHARLEVOIX-SAGUENAY,RECESSIVE SPASTIC ATAXIA,CEREBELLAR-ATAXIA,GENE,PHENOTYPE,DELETION,FAMILY},
  language     = {eng},
  number       = {13},
  pages        = {1181--1188},
  title        = {Mutations in SACS cause atypical and late-onset forms of ARSACS},
  url          = {http://www.neurology.org/content/75/13/1181.full.pdf},
  volume       = {75},
  year         = {2010},
}

Web of Science
Times cited: