Mutations in SACS cause atypical and late-onset forms of ARSACS - PubMed (original) (raw)
. 2010 Sep 28;75(13):1181-8.
doi: 10.1212/WNL.0b013e3181f4d86c.
T Deconinck, K Smets, D Goossens, P Van den Bergh, K Dahan, E Schmedding, P Santens, V Milic Rasic, P Van Damme, W Robberecht, L De Meirleir, B Michielsens, J Del-Favero, A Jordanova, P De Jonghe
Affiliations
- PMID: 20876471
- DOI: 10.1212/WNL.0b013e3181f4d86c
Mutations in SACS cause atypical and late-onset forms of ARSACS
J Baets et al. Neurology. 2010.
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.
Similar articles
- Phenotypic features and genetic findings in sacsin-related autosomal recessive ataxia in Tunisia.
El Euch-Fayache G, Lalani I, Amouri R, Turki I, Ouahchi K, Hung WY, Belal S, Siddique T, Hentati F. El Euch-Fayache G, et al. Arch Neurol. 2003 Jul;60(7):982-8. doi: 10.1001/archneur.60.7.982. Arch Neurol. 2003. PMID: 12873855 - A novel genomic disorder: a deletion of the SACS gene leading to spastic ataxia of Charlevoix-Saguenay.
Breckpot J, Takiyama Y, Thienpont B, Van Vooren S, Vermeesch JR, Ortibus E, Devriendt K. Breckpot J, et al. Eur J Hum Genet. 2008 Sep;16(9):1050-4. doi: 10.1038/ejhg.2008.58. Epub 2008 Apr 9. Eur J Hum Genet. 2008. PMID: 18398442 - [Autosomal recessive spastic ataxia of Charlevoix-Saguenay: study of a family and review of the literature].
Anheim M, Chaigne D, Fleury M, Santorelli FM, De Sèze J, Durr A, Brice A, Koenig M, Tranchant C. Anheim M, et al. Rev Neurol (Paris). 2008 Apr;164(4):363-8. doi: 10.1016/j.neurol.2008.02.001. Epub 2008 Mar 25. Rev Neurol (Paris). 2008. PMID: 18439928 French. - Autosomal recessive spastic ataxia of Charlevoix-Saguenay: an overview.
Bouhlal Y, Amouri R, El Euch-Fayeche G, Hentati F. Bouhlal Y, et al. Parkinsonism Relat Disord. 2011 Jul;17(6):418-22. doi: 10.1016/j.parkreldis.2011.03.005. Epub 2011 Mar 30. Parkinsonism Relat Disord. 2011. PMID: 21450511 Review. - [Spastic ataxia of Charlevoix-Saguenay: the first Russian case report and literature review].
Rudenskaya GE, Kadnikova VA, Ryzhkova OP. Rudenskaya GE, et al. Zh Nevrol Psikhiatr Im S S Korsakova. 2020;120(2):85-91. doi: 10.17116/jnevro202012002185. Zh Nevrol Psikhiatr Im S S Korsakova. 2020. PMID: 32307416 Review. Russian.
Cited by
- SNP Analysis and Whole Exome Sequencing: Their Application in the Analysis of a Consanguineous Pedigree Segregating Ataxia.
Nickerson SL, Marquis-Nicholson R, Claxton K, Ashton F, Leong IU, Prosser DO, Love JM, George AM, Taylor G, Wilson C, Gardner RJ, Love DR. Nickerson SL, et al. Microarrays (Basel). 2015 Oct 23;4(4):490-502. doi: 10.3390/microarrays4040490. Microarrays (Basel). 2015. PMID: 27600236 Free PMC article. - 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, Mihova K, Georgiev M, Ferdinandov D, Bichev S, Kaneva R, Mitev V, Jordanova A, Tournev I. Chamova T, et al. Mol Genet Genomic Med. 2024 Jul;12(7):e2483. doi: 10.1002/mgg3.2483. Mol Genet Genomic Med. 2024. PMID: 39044368 Free PMC article. - Coordination and timing deficits in speech and swallowing in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS).
Vogel AP, Rommel N, Oettinger A, Stoll LH, Kraus EM, Gagnon C, Horger M, Krumm P, Timmann D, Storey E, Schöls L, Synofzik M. Vogel AP, et al. J Neurol. 2018 Sep;265(9):2060-2070. doi: 10.1007/s00415-018-8950-4. Epub 2018 Jul 2. J Neurol. 2018. PMID: 29968200 - Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay without Spasticity.
Aida I, Ozawa T, Fujinaka H, Goto K, Ohta K, Nakajima T. Aida I, et al. Intern Med. 2021 Dec 15;60(24):3963-3967. doi: 10.2169/internalmedicine.7401-21. Epub 2021 Jun 12. Intern Med. 2021. PMID: 34121011 Free PMC article. - Hereditary spastic paraplegias: identification of a novel SPG57 variant affecting TFG oligomerization and description of HSP subtypes in Sudan.
Elsayed LEO, Mohammed IN, Hamed AAA, Elseed MA, Johnson A, Mairey M, Mohamed HESA, Idris MN, Salih MAM, El-Sadig SM, Koko ME, Mohamed AYO, Raymond L, Coutelier M, Darios F, Siddig RA, Ahmed AKMA, Babai AMA, Malik HMO, Omer ZMBM, Mohamed EOE, Eltahir HB, Magboul NAA, Bushara EE, Elnour A, Rahim SMA, Alattaya A, Elbashir MI, Ibrahim ME, Durr A, Audhya A, Brice A, Ahmed AE, Stevanin G. Elsayed LEO, et al. Eur J Hum Genet. 2016 Jan;25(1):100-110. doi: 10.1038/ejhg.2016.108. Epub 2016 Sep 7. Eur J Hum Genet. 2016. PMID: 27601211 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases