Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Neurology
Published in: Journal of Neurology 2/2019

Open Access 01-02-2019 | Neurological Update

Spinocerebellar ataxia: an update

Authors: Roisin Sullivan, Wai Yan Yau, Emer O’Connor, Henry Houlden

Published in: Journal of Neurology | Issue 2/2019

Login to get access

Abstract

Spinocerebellar ataxia (SCA) is a heterogeneous group of neurodegenerative ataxic disorders with autosomal dominant inheritance. We aim to provide an update on the recent clinical and scientific progresses in SCA where numerous novel genes have been identified with next-generation sequencing techniques. The main disease mechanisms of these SCAs include toxic RNA gain-of-function, mitochondrial dysfunction, channelopathies, autophagy and transcription dysregulation. Recent studies have also demonstrated the importance of DNA repair pathways in modifying SCA with CAG expansions. In addition, we summarise the latest technological advances in detecting known and novel repeat expansion in SCA. Finally, we discuss the roles of antisense oligonucleotides and RNA-based therapy as potential treatments.
Appendix
Available only for authorised users
Literature
1.
Paulson HL, Shakkottai VG, Clark HB, Orr HT (2017) Polyglutamine spinocerebellar ataxias—from genes to potential treatments. Nat Rev Neurosci 18(10):613–626CrossRefPubMedPubMedCentral
2.
Ruano L, Melo C, Silva MC, Coutinho P (2014) The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies. Neuroepidemiology 42(3):174–183CrossRefPubMed
3.
de Castilhos RM, Furtado GV, Gheno TC, Schaeffer P, Russo A, Barsottini O et al (2014) Spinocerebellar ataxias in Brazil–frequencies and modulating effects of related genes. Cerebellum 13(1):17–28CrossRefPubMed
4.
Coutinho P, Ruano L, Loureiro JL, Cruz VT, Barros J, Tuna A et al (2013) Hereditary ataxia and spastic paraplegia in Portugal: a population-based prevalence study. JAMA Neurol 70(6):746–755CrossRefPubMed
5.
Zaltzman R, Sharony R, Klein C, Gordon CR (2016) Spinocerebellar ataxia type 3 in Israel: phenotype and genotype of a Jew Yemenite subpopulation. J Neurol 263(11):2207–2214CrossRefPubMed
6.
Gonzalez-Zaldivar Y, Vazquez-Mojena Y, Laffita-Mesa JM, Almaguer-Mederos LE, Rodriguez-Labrada R, Sanchez-Cruz G et al (2015) Epidemiological, clinical, and molecular characterization of Cuban families with spinocerebellar ataxia type 3/Machado–Joseph disease. Cerebellum Ataxias 2:1CrossRefPubMedPubMedCentral
7.
Paradisi I, Ikonomu V, Arias S (2016) Spinocerebellar ataxias in Venezuela: genetic epidemiology and their most likely ethnic descent. J Hum Genet 61(3):215–222CrossRefPubMed
8.
Bargiela D, Yu-Wai-Man P, Keogh M, Horvath R, Chinnery PF (2015) Prevalence of neurogenetic disorders in the North of England. Neurology 85(14):1195–1201CrossRefPubMedPubMedCentral
9.
Coutelier M, Coarelli G, Monin ML, Konop J, Davoine CS, Tesson C et al (2017) A panel study on patients with dominant cerebellar ataxia highlights the frequency of channelopathies. Brain 140(6):1579–1594CrossRefPubMed
10.
Chen Z, Wang P, Wang C, Peng Y, Hou X, Zhou X et al (2018) Updated frequency analysis of spinocerebellar ataxia in China. Brain 141(4):e22CrossRefPubMed
11.
Chelban V, Wiethoff S, Fabian-Jessing BK, Haridy NA, Khan A, Efthymiou S et al. Genotype–phenotype correlations, dystonia and disease progression in spinocerebellar ataxia type 14. Mov Disord. 2018
12.
Aydin G, Dekomien G, Hoffjan S, Gerding WM, Epplen JT, Arning L (2018) Frequency of SCA8, SCA10, SCA12, SCA36, FXTAS and C9orf72 repeat expansions in SCA patients negative for the most common SCA subtypes. BMC Neurol 18(1):3CrossRefPubMedPubMedCentral
13.
Fawcett K, Mehrabian M, Liu YT, Hamed S, Elahi E, Revesz T et al (2013) The frequency of spinocerebellar ataxia type 23 in a UK population. J Neurol 260(3):856–859CrossRefPubMed
14.
Guo YC, Lin JJ, Liao YC, Tsai PC, Lee YC, Soong BW (2014) Spinocerebellar ataxia 35: novel mutations in TGM6 with clinical and genetic characterization. Neurology 83(17):1554–1561CrossRefPubMed
15.
Ngo K, Aker M, Petty LE, Chen J, Cavalcanti F, Nelson AB et al (2018) Expanding the global prevalence of spinocerebellar ataxia type 42. Neurol Genet 4(3):e232CrossRefPubMedPubMedCentral
16.
Obayashi M, Stevanin G, Synofzik M, Monin ML, Duyckaerts C, Sato N et al (2015) Spinocerebellar ataxia type 36 exists in diverse populations and can be caused by a short hexanucleotide GGCCTG repeat expansion. J Neurol Neurosurg Psychiatry 86(9):986–995CrossRefPubMed
17.
18.
Valera JM, Diaz T, Petty LE, Quintans B, Yanez Z, Boerwinkle E et al (2017) Prevalence of spinocerebellar ataxia 36 in a US population. Neurol Genet 3(4):e174CrossRefPubMedPubMedCentral
19.
Harding AE (1982) The clinical features and classification of the late onset autosomal dominant cerebellar ataxias. A study of 11 families, including descendants of the ‘the Drew family of Walworth’. Brain 105(Pt 1):1–28CrossRefPubMed
20.
Bird TD (1993) Hereditary ataxia overview. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K et al (eds) GeneReviews((R)). Seattle (WA)
21.
Winkelmann J, Lin L, Schormair B, Kornum BR, Faraco J, Plazzi G et al (2012) Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy. Hum Mol Genet 21(10):2205–2210CrossRefPubMedPubMedCentral
22.
Pfeffer G, Blakely EL, Alston CL, Hassani A, Boggild M, Horvath R et al (2012) Adult-onset spinocerebellar ataxia syndromes due to MTATP6 mutations. J Neurol Neurosurg Psychiatry 83(9):883–886CrossRefPubMed
23.
Gennarino VA, Palmer EE, McDonell LM, Wang L, Adamski CJ, Koire A et al (2018) A Mild PUM1 mutation is associated with adult-onset ataxia, whereas haploinsufficiency causes developmental delay and seizures. Cell 172(5):924–936 e11CrossRefPubMedPubMedCentral
24.
Nibbeling EAR, Duarri A, Verschuuren-Bemelmans CC, Fokkens MR, Karjalainen JM, Smeets C et al (2017) Exome sequencing and network analysis identifies shared mechanisms underlying spinocerebellar ataxia. Brain 140(11):2860–2878CrossRefPubMed
25.
Holmes SE, O’Hearn EE, McInnis MG, Gorelick-Feldman DA, Kleiderlein JJ, Callahan C et al (1999) Expansion of a novel CAG trinucleotide repeat in the 5′ region of PPP2R2B is associated with SCA12. Nat Genet 23(4):391–392CrossRefPubMed
26.
Synofzik M, Beetz C, Bauer C, Bonin M, Sanchez-Ferrero E, Schmitz-Hubsch T et al (2011) Spinocerebellar ataxia type 15: diagnostic assessment, frequency, and phenotypic features. J Med Genet 48(6):407–412CrossRefPubMed
27.
van Swieten JC, Brusse E, de Graaf BM, Krieger E, van de Graaf R, de Koning I et al (2003) A mutation in the fibroblast growth factor 14 gene is associated with autosomal dominant cerebellar ataxia [corrected]. Am J Hum Genet 72(1):191–199CrossRefPubMed
28.
Chen DH, Brkanac Z, Verlinde CL, Tan XJ, Bylenok L, Nochlin D et al (2003) Missense mutations in the regulatory domain of PKC gamma: a new mechanism for dominant nonepisodic cerebellar ataxia. Am J Hum Genet 72(4):839–849CrossRefPubMedPubMedCentral
29.
Kobayashi H, Abe K, Matsuura T, Ikeda Y, Hitomi T, Akechi Y et al (2011) Expansion of intronic GGCCTG hexanucleotide repeat in NOP56 causes SCA36, a type of spinocerebellar ataxia accompanied by motor neuron involvement. Am J Hum Genet 89(1):121–130CrossRefPubMedPubMedCentral
30.
Rossi M, Perez-Lloret S, Doldan L, Cerquetti D, Balej J, Millar Vernetti P et al (2014) Autosomal dominant cerebellar ataxias: a systematic review of clinical features. Eur J Neurol 21(4):607–615CrossRefPubMed
31.
Marras C, Lang A, van de Warrenburg BP, Sue CM, Tabrizi SJ, Bertram L et al (2016) Nomenclature of genetic movement disorders: recommendations of the international Parkinson and movement disorder society task force. Mov Disord 31(4):436–457CrossRefPubMed
32.
Pena LDM, Jiang YH, Schoch K, Spillmann RC, Walley N, Stong N et al (2018) Looking beyond the exome: a phenotype-first approach to molecular diagnostic resolution in rare and undiagnosed diseases. Genet Med 20(4):464–469CrossRefPubMed
33.
Jen JC, Graves TD, Hess EJ, Hanna MG, Griggs RC, Baloh RW et al (2007) Primary episodic ataxias: diagnosis, pathogenesis and treatment. Brain 130(Pt 10):2484–2493CrossRefPubMed
34.
Graves TD, Cha YH, Hahn AF, Barohn R, Salajegheh MK, Griggs RC et al (2014) Episodic ataxia type 1: clinical characterization, quality of life and genotype–phenotype correlation. Brain 137(Pt 4):1009–1018CrossRefPubMedPubMedCentral
35.
Jen J, Kim GW, Baloh RW (2004) Clinical spectrum of episodic ataxia type 2. Neurology 62(1):17–22CrossRefPubMed
36.
Tsoi H, Yu AC, Chen ZS, Ng NK, Chan AY, Yuen LY et al (2014) A novel missense mutation in CCDC88C activates the JNK pathway and causes a dominant form of spinocerebellar ataxia. J Med Genet 51(9):590–595CrossRefPubMed
37.
Fogel BL, Hanson SM, Becker EB (2015) Do mutations in the murine ataxia gene TRPC3 cause cerebellar ataxia in humans? Mov Disord 30(2):284–286CrossRefPubMed
38.
Morino H, Matsuda Y, Muguruma K, Miyamoto R, Ohsawa R, Ohtake T et al (2015) A mutation in the low voltage-gated calcium channel CACNA1G alters the physiological properties of the channel, causing spinocerebellar ataxia. Mol Brain 8:89CrossRefPubMedPubMedCentral
39.
Depondt C, Donatello S, Rai M, Wang FC, Manto M, Simonis N et al (2016) MME mutation in dominant spinocerebellar ataxia with neuropathy (SCA43). Neurol Genet 2(5):e94CrossRefPubMedPubMedCentral
40.
Watson LM, Bamber E, Schnekenberg RP, Williams J, Bettencourt C, Lickiss J et al (2017) Dominant mutations in GRM1 cause spinocerebellar ataxia type 44. Am J Hum Genet 101(3):451–458CrossRefPubMedPubMedCentral
41.
Coutelier M, Stevanin G, Brice A (2015) Genetic landscape remodelling in spinocerebellar ataxias: the influence of next-generation sequencing. J Neurol 262(10):2382–2395CrossRefPubMed
42.
Galatolo D, Tessa A, Filla A, Santorelli FM (2018) Clinical application of next generation sequencing in hereditary spinocerebellar ataxia: increasing the diagnostic yield and broadening the ataxia-spasticity spectrum. A retrospective analysis. Neurogenetics 19(1):1–8CrossRefPubMed
43.
Coutelier M, Hammer MB, Stevanin G, Monin ML, Davoine CS, Mochel F et al (2018) Efficacy of exome-targeted capture sequencing to detect mutations in known cerebellar ataxia genes. JAMA Neurol 75(5):591–599CrossRefPubMedPubMedCentral
44.
45.
Lin X, Ashizawa T (2005) Recent progress in spinocerebellar ataxia type-10 (SCA10). Cerebellum 4(1):37–42CrossRefPubMed
46.
White M, Xia G, Gao R, Wakamiya M, Sarkar PS, McFarland K et al (2012) Transgenic mice with SCA10 pentanucleotide repeats show motor phenotype and susceptibility to seizure: a toxic RNA gain-of-function model. J Neurosci Res 90(3):706–714CrossRefPubMed
47.
Daughters RS, Tuttle DL, Gao W, Ikeda Y, Moseley ML, Ebner TJ et al (2009) RNA gain-of-function in spinocerebellar ataxia type 8. PLoS Genet 5(8):e1000600CrossRefPubMedPubMedCentral
48.
Cho DH, Thienes CP, Mahoney SE, Analau E, Filippova GN, Tapscott SJ (2005) Antisense transcription and heterochromatin at the DM1 CTG repeats are constrained by CTCF. Mol Cell 20(3):483–489CrossRefPubMed
49.
Rudnicki DD, Holmes SE, Lin MW, Thornton CA, Ross CA, Margolis RL (2007) Huntington’s disease-like 2 is associated with CUG repeat-containing RNA foci. Ann Neurol 61(3):272–282CrossRefPubMed
50.
Corral-Juan M, Serrano-Munuera C, Rabano A, Cota-Gonzalez D, Segarra-Roca A, Ispierto L et al (2018) Clinical, genetic and neuropathological characterization of spinocerebellar ataxia type 37. Brain 141(7):1981–1997CrossRefPubMed
51.
McBride HM, Neuspiel M, Wasiak S (2006) Mitochondria: more than just a powerhouse. Curr Biol 16(14):R551–R560CrossRefPubMed
52.
Cornelius N, Wardman JH, Hargreaves IP, Neergheen V, Bie AS, Tumer Z et al (2017) Evidence of oxidative stress and mitochondrial dysfunction in spinocerebellar ataxia type 2 (SCA2) patient fibroblasts: effect of coenzyme Q10 supplementation on these parameters. Mitochondrion 34:103–114CrossRefPubMed
53.
Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39(1):44–84CrossRefPubMed
54.
Simon DK, Zheng K, Velazquez L, Santos N, Almaguer L, Figueroa KP et al (2007) Mitochondrial complex I gene variant associated with early age at onset in spinocerebellar ataxia type 2. Arch Neurol 64(7):1042–1044CrossRefPubMed
55.
Monte TL, Pereira FS, Reckziegel EDR, Augustin MC, Locks-Coelho LD, Santos ASP et al (2017) Neurological phenotypes in spinocerebellar ataxia type 2: role of mitochondrial polymorphism A10398G and other risk factors. Parkinsonism Relat Disord 42:54–60CrossRefPubMed
56.
57.
Coutelier M, Blesneac I, Monteil A, Monin ML, Ando K, Mundwiller E et al (2015) A recurrent mutation in CACNA1G alters Cav3.1 T-type calcium-channel conduction and causes autosomal-dominant cerebellar ataxia. Am J Hum Genet 97(5):726–737CrossRefPubMedPubMedCentral
58.
59.
Alves S, Cormier-Dequaire F, Marinello M, Marais T, Muriel MP, Beaumatin F et al (2014) The autophagy/lysosome pathway is impaired in SCA7 patients and SCA7 knock-in mice. Acta Neuropathol 128(5):705–722CrossRefPubMed
60.
Onofre I, Mendonca N, Lopes S, Nobre R, de Melo JB, Carreira IM et al (2016) Fibroblasts of Machado Joseph disease patients reveal autophagy impairment. Sci Rep 6:28220CrossRefPubMedPubMedCentral
61.
Menzies FM, Huebener J, Renna M, Bonin M, Riess O, Rubinsztein DC (2010) Autophagy induction reduces mutant ataxin-3 levels and toxicity in a mouse model of spinocerebellar ataxia type 3. Brain 133(Pt 1):93–104CrossRefPubMed
62.
Ashkenazi A, Bento CF, Ricketts T, Vicinanza M, Siddiqi F, Pavel M et al (2017) Polyglutamine tracts regulate beclin 1-dependent autophagy. Nature 545(7652):108–111CrossRefPubMedPubMedCentral
63.
Matilla-Duenas A, Sanchez I, Corral-Juan M, Davalos A, Alvarez R, Latorre P (2010) Cellular and molecular pathways triggering neurodegeneration in the spinocerebellar ataxias. Cerebellum 9(2):148–166CrossRefPubMed
64.
Mushegian AR, Bassett DE Jr, Boguski MS, Bork P, Koonin EV (1997) Positionally cloned human disease genes: patterns of evolutionary conservation and functional motifs. Proc Natl Acad Sci USA 94(11):5831–5836CrossRefPubMedPubMedCentral
65.
66.
Genetic Modifiers of Huntington’s Disease C (2015) Identification of Genetic Factors that Modify Clinical Onset of Huntington’s Disease. Cell 162(3):516–526CrossRef
67.
Bettencourt C, Hensman-Moss D, Flower M, Wiethoff S, Brice A, Goizet C et al (2016) DNA repair pathways underlie a common genetic mechanism modulating onset in polyglutamine diseases. Ann Neurol 79(6):983–990CrossRefPubMedPubMedCentral
68.
Thongthip S, Bellani M, Gregg SQ, Sridhar S, Conti BA, Chen Y et al (2016) Fan1 deficiency results in DNA interstrand cross-link repair defects, enhanced tissue karyomegaly, and organ dysfunction. Genes Dev 30(6):645–659CrossRefPubMedPubMedCentral
69.
Trinh TQ, Sinden RR (1991) Preferential DNA secondary structure mutagenesis in the lagging strand of replication in E. coli. Nature 352(6335):544–547CrossRefPubMed
70.
Martins S, Pearson CE, Coutinho P, Provost S, Amorim A, Dube MP et al (2014) Modifiers of (CAG)(n) instability in Machado-Joseph disease (MJD/SCA3) transmissions: an association study with DNA replication, repair and recombination genes. Hum Genet 133(10):1311–1318CrossRefPubMed
71.
72.
Raczy C, Petrovski R, Saunders CT, Chorny I, Kruglyak S, Margulies EH et al (2013) Isaac: ultra-fast whole-genome secondary analysis on Illumina sequencing platforms. Bioinformatics 29(16):2041–2043CrossRefPubMed
73.
Akimoto C, Volk AE, van Blitterswijk M, Van den Broeck M, Leblond CS, Lumbroso S et al (2014) A blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratories. J Med Genet 51(6):419–424CrossRefPubMed
74.
Ashley EA (2015) The precision medicine initiative: a new national effort. JAMA 313(21):2119–2120CrossRefPubMed
75.
Cagnoli C, Brussino A, Mancini C, Ferrone M, Orsi L, Salmin P et al (2018) Spinocerebellar ataxia tethering PCR: a rapid genetic test for the diagnosis of spinocerebellar ataxia types 1, 2, 3, 6, and 7 by PCR and capillary electrophoresis. J Mol Diagn 20(3):289–297CrossRefPubMed
76.
Clarke J, Wu HC, Jayasinghe L, Patel A, Reid S, Bayley H (2009) Continuous base identification for single-molecule nanopore DNA sequencing. Nat Nanotechnol 4(4):265–270CrossRefPubMed
77.
78.
Carneiro MO, Russ C, Ross MG, Gabriel SB, Nusbaum C, DePristo MA (2012) Pacific biosciences sequencing technology for genotyping and variation discovery in human data. BMC Genom 13:375CrossRef
79.
Laver T, Harrison J, O’Neill PA, Moore K, Farbos A, Paszkiewicz K et al (2015) Assessing the performance of the Oxford Nanopore Technologies MinION. Biomol Detect Quantif 3:1–8CrossRefPubMedPubMedCentral
80.
Dolzhenko E, van Vugt J, Shaw RJ, Bekritsky MA, van Blitterswijk M, Narzisi G et al (2017) Detection of long repeat expansions from PCR-free whole-genome sequence data. Genome Res 27(11):1895–1903CrossRefPubMedPubMedCentral
81.
82.
83.
Geary RS, Norris D, Yu R, Bennett CF (2015) Pharmacokinetics, biodistribution and cell uptake of antisense oligonucleotides. Adv Drug Deliv Rev 87:46–51CrossRefPubMed
84.
Toonen LJ, Schmidt I, Luijsterburg MS, van Attikum H, van Roon-Mom WM (2016) Antisense oligonucleotide-mediated exon skipping as a strategy to reduce proteolytic cleavage of ataxin-3. Sci Rep 6:35200CrossRefPubMedPubMedCentral
85.
Evers MM, Tran HD, Zalachoras I, Pepers BA, Meijer OC, den Dunnen JT et al (2013) Ataxin-3 protein modification as a treatment strategy for spinocerebellar ataxia type 3: removal of the CAG containing exon. Neurobiol Dis 58:49–56CrossRefPubMed
86.
Moore LR, Rajpal G, Dillingham IT, Qutob M, Blumenstein KG, Gattis D et al (2017) Evaluation of antisense oligonucleotides Targeting ATXN3 in SCA3 mouse models. Mol Ther Nucleic Acids 7:200–210CrossRefPubMedPubMedCentral
87.
Toonen LJA, Rigo F, van Attikum H, van Roon-Mom WMC (2017) Antisense oligonucleotide-mediated removal of the polyglutamine repeat in spinocerebellar ataxia type 3 mice. Mol Ther Nucleic Acids 8:232–242CrossRefPubMedPubMedCentral
88.
Becker LA, Huang B, Bieri G, Ma R, Knowles DA, Jafar-Nejad P et al (2017) Therapeutic reduction of ataxin-2 extends lifespan and reduces pathology in TDP-43 mice. Nature 544(7650):367–371CrossRefPubMedPubMedCentral
89.
90.
Ramachandran PS, Boudreau RL, Schaefer KA, La Spada AR, Davidson BL (2014) Nonallele specific silencing of ataxin-7 improves disease phenotypes in a mouse model of SCA7. Mol Ther 22(9):1635–1642CrossRefPubMedPubMedCentral
91.
Scholefield J, Greenberg LJ, Weinberg MS, Arbuthnot PB, Abdelgany A, Wood MJ (2009) Design of RNAi hairpins for mutation-specific silencing of ataxin-7 and correction of a SCA7 phenotype. PLoS One 4(9):e7232CrossRefPubMedPubMedCentral
92.
Nobrega C, Nascimento-Ferreira I, Onofre I, Albuquerque D, Hirai H, Deglon N et al (2013) Silencing mutant ataxin-3 rescues motor deficits and neuropathology in Machado-Joseph disease transgenic mice. PLoS One 8(1):e52396CrossRefPubMedPubMedCentral
93.
Costa Mdo C, Luna-Cancalon K, Fischer S, Ashraf NS, Ouyang M, Dharia RM et al (2013) Toward RNAi therapy for the polyglutamine disease Machado–Joseph disease. Mol Ther 21(10):1898–1908CrossRefPubMed
94.
Weimann JM, Charlton CA, Brazelton TR, Hackman RC, Blau HM (2003) Contribution of transplanted bone marrow cells to Purkinje neurons in human adult brains. Proc Natl Acad Sci USA 100(4):2088–2093CrossRefPubMedPubMedCentral
95.
Fernandez-Funez P, Nino-Rosales ML, de Gouyon B, She WC, Luchak JM, Martinez P et al (2000) Identification of genes that modify ataxin-1-induced neurodegeneration. Nature 408(6808):101–106CrossRefPubMed
96.
Chen KA, Cruz PE, Lanuto DJ, Flotte TR, Borchelt DR, Srivastava A et al (2011) Cellular fusion for gene delivery to SCA1 affected Purkinje neurons. Mol Cell Neurosci 47(1):61–70CrossRefPubMedPubMedCentral
97.
Chintawar S, Hourez R, Ravella A, Gall D, Orduz D, Rai M et al (2009) Grafting neural precursor cells promotes functional recovery in an SCA1 mouse model. J Neurosci 29(42):13126–13135CrossRefPubMedPubMedCentral
98.
Alvarez-Dolado M, Pardal R, Garcia-Verdugo JM, Fike JR, Lee HO, Pfeffer K et al (2003) Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature 425(6961):968–973CrossRefPubMed
99.
Chang YK, Chen MH, Chiang YH, Chen YF, Ma WH, Tseng CY et al (2011) Mesenchymal stem cell transplantation ameliorates motor function deterioration of spinocerebellar ataxia by rescuing cerebellar Purkinje cells. J Biomed Sci 18:54CrossRefPubMedPubMedCentral
100.
Jin JL, Liu Z, Lu ZJ, Guan DN, Wang C, Chen ZB et al (2013) Safety and efficacy of umbilical cord mesenchymal stem cell therapy in hereditary spinocerebellar ataxia. Curr Neurovasc Res 10(1):11–20CrossRefPubMed
101.
Dongmei H, Jing L, Mei X, Ling Z, Hongmin Y, Zhidong W et al (2011) Clinical analysis of the treatment of spinocerebellar ataxia and multiple system atrophy-cerebellar type with umbilical cord mesenchymal stromal cells. Cytotherapy 13(8):913–917CrossRefPubMed
102.
Orr HT, Chung MY, Banfi S, Kwiatkowski TJ Jr, Servadio A, Beaudet AL et al (1993) Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1. Nat Genet 4(3):221–226CrossRefPubMed
103.
Pulst SM, Nechiporuk A, Nechiporuk T, Gispert S, Chen XN, Lopes-Cendes I et al (1996) Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2. Nat Genet 14(3):269–276CrossRefPubMed
104.
Kawaguchi Y, Okamoto T, Taniwaki M, Aizawa M, Inoue M, Katayama S et al (1994) CAG expansions in a novel gene for Machado–Joseph disease at chromosome 14q32.1. Nat Genet 8(3):221–228CrossRefPubMed
105.
Flanigan K, Gardner K, Alderson K, Galster B, Otterud B, Leppert MF et al (1996) Autosomal dominant spinocerebellar ataxia with sensory axonal neuropathy (SCA4): clinical description and genetic localization to chromosome 16q22.1. Am J Hum Genet 59(2):392–399PubMedPubMedCentral
106.
Ranum LP, Schut LJ, Lundgren JK, Orr HT, Livingston DM (1994) Spinocerebellar ataxia type 5 in a family descended from the grandparents of President Lincoln maps to chromosome 11. Nat Genet 8(3):280–284CrossRefPubMed
107.
Zhuchenko O, Bailey J, Bonnen P, Ashizawa T, Stockton DW, Amos C et al (1997) Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel. Nat Genet 15(1):62–69CrossRefPubMed
108.
Trottier Y, Lutz Y, Stevanin G, Imbert G, Devys D, Cancel G et al (1995) Polyglutamine expansion as a pathological epitope in Huntington’s disease and four dominant cerebellar ataxias. Nature 378(6555):403–406CrossRefPubMed
109.
Koob MD, Moseley ML, Schut LJ, Benzow KA, Bird TD, Day JW et al (1999) An untranslated CTG expansion causes a novel form of spinocerebellar ataxia (SCA8). Nat Genet 21(4):379–384CrossRefPubMed
110.
Matsuura T, Yamagata T, Burgess DL, Rasmussen A, Grewal RP, Watase K et al (2000) Large expansion of the ATTCT pentanucleotide repeat in spinocerebellar ataxia type 10. Nat Genet 26(2):191–194CrossRefPubMed
111.
Houlden H, Johnson J, Gardner-Thorpe C, Lashley T, Hernandez D, Worth P et al (2007) Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation, segregate with spinocerebellar ataxia type 11. Nat Genet 39(12):1434–1436CrossRefPubMed
112.
Waters MF, Minassian NA, Stevanin G, Figueroa KP, Bannister JP, Nolte D et al (2006) Mutations in voltage-gated potassium channel KCNC3 cause degenerative and developmental central nervous system phenotypes. Nat Genet 38(4):447–451CrossRefPubMed
113.
Brkanac Z, Bylenok L, Fernandez M, Matsushita M, Lipe H, Wolff J et al (2002) A new dominant spinocerebellar ataxia linked to chromosome 19q13.4-qter. Arch Neurol 59(8):1291–1295CrossRefPubMed
114.
van de Leemput J, Chandran J, Knight MA, Holtzclaw LA, Scholz S, Cookson MR et al (2007) Deletion at ITPR1 underlies ataxia in mice and spinocerebellar ataxia 15 in humans. PLoS Genet 3(6):e108CrossRefPubMedPubMedCentral
115.
Miyoshi Y, Yamada T, Tanimura M, Taniwaki T, Arakawa K, Ohyagi Y et al (2001) A novel autosomal dominant spinocerebellar ataxia (SCA16) linked to chromosome 8q22.1-24.1. Neurology 57(1):96–100CrossRefPubMed
116.
Koide R, Kobayashi S, Shimohata T, Ikeuchi T, Maruyama M, Saito M et al (1999) A neurological disease caused by an expanded CAG trinucleotide repeat in the TATA-binding protein gene: a new polyglutamine disease? Hum Mol Genet 8(11):2047–2053CrossRefPubMed
117.
Brkanac Z, Fernandez M, Matsushita M, Lipe H, Wolff J, Bird TD et al (2002) Autosomal dominant sensory/motor neuropathy with Ataxia (SMNA): Linkage to chromosome 7q22-q32. Am J Med Genet 114(4):450–457CrossRefPubMed
118.
Schelhaas HJ, Ippel PF, Hageman G, Sinke RJ, van der Laan EN, Beemer FA (2001) Clinical and genetic analysis of a four-generation family with a distinct autosomal dominant cerebellar ataxia. J Neurol 248(2):113–120CrossRefPubMed
119.
Knight MA, Gardner RJ, Bahlo M, Matsuura T, Dixon JA, Forrest SM et al (2004) Dominantly inherited ataxia and dysphonia with dentate calcification: spinocerebellar ataxia type 20. Brain 127(Pt 5):1172–1181CrossRefPubMed
120.
Devos D, Schraen-Maschke S, Vuillaume I, Dujardin K, Naze P, Willoteaux C et al (2001) Clinical features and genetic analysis of a new form of spinocerebellar ataxia. Neurology 56(2):234–238CrossRefPubMed
121.
Verbeek DS, van de Warrenburg BP, Wesseling P, Pearson PL, Kremer HP, Sinke RJ (2004) Mapping of the SCA23 locus involved in autosomal dominant cerebellar ataxia to chromosome region 20p13-12.3. Brain 127(Pt 11):2551–2557CrossRefPubMed
122.
Stevanin G, Bouslam N, Thobois S, Azzedine H, Ravaux L, Boland A et al (2004) Spinocerebellar ataxia with sensory neuropathy (SCA25) maps to chromosome 2p. Ann Neurol 55(1):97–104CrossRefPubMed
123.
Yu GY, Howell MJ, Roller MJ, Xie TD, Gomez CM (2005) Spinocerebellar ataxia type 26 maps to chromosome 19p13.3 adjacent to SCA6. Ann Neurol 57(3):349–354CrossRefPubMed
124.
Svenstrup K, Nielsen TT, Aidt F, Rostgaard N, Duno M, Wibrand F et al (2017) SCA28: novel mutation in the AFG3L2 proteolytic domain causes a mild cerebellar syndrome with selective type-1 muscle fiber atrophy. Cerebellum 16(1):62–67CrossRefPubMed
125.
Dudding TE, Friend K, Schofield PW, Lee S, Wilkinson IA, Richards RI (2004) Autosomal dominant congenital non-progressive ataxia overlaps with the SCA15 locus. Neurology 63(12):2288–2292CrossRefPubMed
126.
Storey E, Bahlo M, Fahey M, Sisson O, Lueck CJ, Gardner RJ (2009) A new dominantly inherited pure cerebellar ataxia, SCA 30. J Neurol Neurosurg Psychiatry 80(4):408–411CrossRefPubMed
127.
Nagaoka U, Takashima M, Ishikawa K, Yoshizawa K, Yoshizawa T, Ishikawa M et al (2000) A gene on SCA4 locus causes dominantly inherited pure cerebellar ataxia. Neurology 54(10):1971–1975CrossRefPubMed
128.
Cadieux-Dion M, Turcotte-Gauthier M, Noreau A, Martin C, Meloche C, Gravel M et al (2014) Expanding the clinical phenotype associated with ELOVL4 mutation: study of a large French-Canadian family with autosomal dominant spinocerebellar ataxia and erythrokeratodermia. JAMA Neurol 71(4):470–475CrossRefPubMed
129.
Wang JL, Yang X, Xia K, Hu ZM, Weng L, Jin X et al (2010) TGM6 identified as a novel causative gene of spinocerebellar ataxias using exome sequencing. Brain 133(Pt 12):3510–3518CrossRefPubMed
130.
Serrano-Munuera C, Corral-Juan M, Stevanin G, San Nicolas H, Roig C, Corral J et al (2013) New subtype of spinocerebellar ataxia with altered vertical eye movements mapping to chromosome 1p32. JAMA Neurol 70(6):764–771CrossRefPubMed
131.
Di Gregorio E, Borroni B, Giorgio E, Lacerenza D, Ferrero M, Lo Buono N et al (2014) ELOVL5 mutations cause spinocerebellar ataxia 38. Am J Hum Genet 95(2):209–217CrossRefPubMedPubMedCentral
132.
Koide R, Ikeuchi T, Onodera O, Tanaka H, Igarashi S, Endo K et al (1994) Unstable expansion of CAG repeat in hereditary dentatorubral–pallidoluysian atrophy (DRPLA). Nat Genet 6(1):9–13CrossRefPubMed
133.
Klein CJ, Botuyan MV, Wu Y, Ward CJ, Nicholson GA, Hammans S et al (2011) Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss. Nat Genet 43(6):595–600CrossRefPubMedPubMedCentral
Metadata
Title
Spinocerebellar ataxia: an update
Authors
Roisin Sullivan
Wai Yan Yau
Emer O’Connor
Henry Houlden
Publication date
01-02-2019
Publisher
Springer Berlin Heidelberg
Published in
Journal of Neurology / Issue 2/2019
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-018-9076-4

Other articles of this Issue 2/2019

Journal of Neurology 2/2019 Go to the issue

Original Communication

Recessive PYROXD1 mutations cause adult-onset limb-girdle-type muscular dystrophy

Original Communication

The applause sign in frontotemporal lobar degeneration and related conditions

Original Communication

Characteristics of single ocular motor nerve palsy associated with anti-GQ1b antibody

Original Communication

Patient characteristics and outcome associations in AMPA receptor encephalitis

Journal club

Imaging in the diagnosis of progressive supranuclear palsy

Original Communication

Predictors and outcome of status epilepticus in cerebral venous thrombosis