5v46

Structural highlights

Disease

[SACS_HUMAN] Defects in SACS are the cause of spastic ataxia Charlevoix-Saguenay type (SACS) [MIM:270550]. It is a neurodegenerative disease characterized by early-onset cerebellar ataxia, spasticity, retinal hypermyelination, pyramidal signs, and both axonal and demyelinating neuropathy with loss of sensory nerve conduction and reduced motor conduction velocities. Other features include dysarthria, distal muscle wasting, nystagmus, defect in conjugate pursuit ocular movements, retinal striation (from prominent retinal nerves) obscuring the retinal blood vessels in places, and the frequent presence of mitral valve prolapse.^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13]}

Function

[SACS_HUMAN] Co-chaperone which acts as a regulator of the Hsp70 chaperone machinery and may be involved in the processing of other ataxia-linked proteins.^[14]

References

1. ↑ Engert JC, Berube P, Mercier J, Dore C, Lepage P, Ge B, Bouchard JP, Mathieu J, Melancon SB, Schalling M, Lander ES, Morgan K, Hudson TJ, Richter A. ARSACS, a spastic ataxia common in northeastern Quebec, is caused by mutations in a new gene encoding an 11.5-kb ORF. Nat Genet. 2000 Feb;24(2):120-5. PMID:10655055 doi:10.1038/72769
2. ↑ Bouhlal Y, El Euch-Fayeche G, Hentati F, Amouri R. A novel SACS gene mutation in a Tunisian family. J Mol Neurosci. 2009 Nov;39(3):333-6. doi: 10.1007/s12031-009-9212-9. Epub 2009, Jun 16. PMID:19529988 doi:10.1007/s12031-009-9212-9
3. ↑ El Euch-Fayache G, Lalani I, Amouri R, Turki I, Ouahchi K, Hung WY, Belal S, Siddique T, Hentati F. Phenotypic features and genetic findings in sacsin-related autosomal recessive ataxia in Tunisia. Arch Neurol. 2003 Jul;60(7):982-8. PMID:12873855 doi:10.1001/archneur.60.7.982
4. ↑ Richter AM, Ozgul RK, Poisson VC, Topaloglu H. Private SACS mutations in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) families from Turkey. Neurogenetics. 2004 Sep;5(3):165-70. Epub 2004 May 20. PMID:15156359 doi:10.1007/s10048-004-0179-y
5. ↑ Ogawa T, Takiyama Y, Sakoe K, Mori K, Namekawa M, Shimazaki H, Nakano I, Nishizawa M. Identification of a SACS gene missense mutation in ARSACS. Neurology. 2004 Jan 13;62(1):107-9. PMID:14718708
6. ↑ Criscuolo C, Sacca F, De Michele G, Mancini P, Combarros O, Infante J, Garcia A, Banfi S, Filla A, Berciano J. Novel mutation of SACS gene in a Spanish family with autosomal recessive spastic ataxia. Mov Disord. 2005 Oct;20(10):1358-61. PMID:16007637 doi:10.1002/mds.20579
7. ↑ Shimazaki H, Takiyama Y, Sakoe K, Ando Y, Nakano I. A phenotype without spasticity in sacsin-related ataxia. Neurology. 2005 Jun 28;64(12):2129-31. PMID:15985586 doi:10.1212/01.WNL.0000166031.91514.B3
8. ↑ Takado Y, Hara K, Shimohata T, Tokiguchi S, Onodera O, Nishizawa M. New mutation in the non-gigantic exon of SACS in Japanese siblings. Mov Disord. 2007 Apr 15;22(5):748-9. PMID:17290461 doi:10.1002/mds.21365
9. ↑ Breckpot J, Takiyama Y, Thienpont B, Van Vooren S, Vermeesch JR, Ortibus E, Devriendt K. A novel genomic disorder: a deletion of the SACS gene leading to spastic ataxia of Charlevoix-Saguenay. Eur J Hum Genet. 2008 Sep;16(9):1050-4. doi: 10.1038/ejhg.2008.58. Epub 2008 Apr , 9. PMID:18398442 doi:10.1038/ejhg.2008.58
10. ↑ Kamada S, Okawa S, Imota T, Sugawara M, Toyoshima I. Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS): novel compound heterozygous mutations in the SACS gene. J Neurol. 2008 Jun;255(6):803-6. doi: 10.1007/s00415-008-0672-6. Epub 2008 May, 19. PMID:18484239 doi:10.1007/s00415-008-0672-6
11. ↑ Ouyang Y, Segers K, Bouquiaux O, Wang FC, Janin N, Andris C, Shimazaki H, Sakoe K, Nakano I, Takiyama Y. Novel SACS mutation in a Belgian family with sacsin-related ataxia. J Neurol Sci. 2008 Jan 15;264(1-2):73-6. Epub 2007 Aug 22. PMID:17716690 doi:10.1016/j.jns.2007.07.022
12. ↑ Vermeer S, Meijer RP, Pijl BJ, Timmermans J, Cruysberg JR, Bos MM, Schelhaas HJ, van de Warrenburg BP, Knoers NV, Scheffer H, Kremer B. ARSACS in the Dutch population: a frequent cause of early-onset cerebellar ataxia. Neurogenetics. 2008 Jul;9(3):207-14. doi: 10.1007/s10048-008-0131-7. Epub 2008, May 9. PMID:18465152 doi:10.1007/s10048-008-0131-7
13. ↑ Baets J, Deconinck T, Smets K, Goossens D, Van den Bergh P, Dahan K, Schmedding E, Santens P, Rasic VM, Van Damme P, Robberecht W, De Meirleir L, Michielsens B, Del-Favero J, Jordanova A, De Jonghe P. Mutations in SACS cause atypical and late-onset forms of ARSACS. Neurology. 2010 Sep 28;75(13):1181-8. doi: 10.1212/WNL.0b013e3181f4d86c. PMID:20876471 doi:10.1212/WNL.0b013e3181f4d86c
14. ↑ Parfitt DA, Michael GJ, Vermeulen EG, Prodromou NV, Webb TR, Gallo JM, Cheetham ME, Nicoll WS, Blatch GL, Chapple JP. The ataxia protein sacsin is a functional co-chaperone that protects against polyglutamine-expanded ataxin-1. Hum Mol Genet. 2009 May 1;18(9):1556-65. doi: 10.1093/hmg/ddp067. Epub 2009 Feb, 10. PMID:19208651 doi:10.1093/hmg/ddp067