Abstract
Background & Objective: The autosomal dominant spinocerebellar ataxias (SCAs) belong to a large and expanding group of neurodegenerative disorders. SCAs comprise more than 40 subtypes characterized by progressive ataxia as a common feature. The most prevalent diseases among SCAs are caused by CAG repeat expansions in the coding-region of the causative gene resulting in polyglutamine (polyQ) tract formation in the encoded protein. Unfortunately, there is no approved therapy to treat cerebellar motor dysfunction in SCA patients. In recent years, several studies have been conducted to recognize the clinical and pathophysiological aspects of the polyQ SCAs more accurately. This scientific progress has provided new opportunities to develop promising gene therapies, including RNA interference and antisense oligonucleotides.
Conclusion: The aim of the current work is to give a brief summary of the clinical features of SCAs and to review the cardinal points of pathomechanisms of the most common polyQ SCAs. In addition, we review the last few year’s promising gene suppression therapies of the most frequent polyQ SCAs in animal models, on the basis of which human trials may be initiated in the near future.
Keywords: Spinocerebellar ataxia, dominant ataxia, hereditary ataxia, ataxia, neurodegenerative diseases, antisense oligonucleotides, RNA therapeutics.
Graphical Abstract
[1]
Ruano L, Melo C, Silva MC, Coutinho P. The global epidemiology of hereditary ataxia and spastic paraplegia: A systematic review of prevalence studies. Neuroepidemiology 2014; 42: 174-83.
[2]
Durr A. Autosomal dominant cerebellar ataxias: Polyglutamine expansions and beyond. Lancet Neurol 2010; 9: 885-94.
[3]
Ashizawa T, Öz G, Paulson HL. Spinocerebellar ataxias: Prospects and challenges for therapy development. Nat Rev Neurol 2018.
[http://dx.doi.org/10.1038/s41582-018-0051-6]
[http://dx.doi.org/10.1038/s41582-018-0051-6]
[4]
Sun YM, Lu C, Wu ZY. Spinocerebellar ataxia: Relationship between phenotype and genotype-a review. Clin Genet 2016; 90: 305-14.
[5]
Campuzano V, Montermini L, Molto MD, et al. Friedreich’s ataxia: Autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 1996; 271: 1423-7.
[6]
Paulson HL, Shakkottai VG, Clark HB, Orr HT. Polyglutamine spinocerebellar ataxias - from genes to potential treatments. Nat Rev Neurosci 2017; 18: 613-26.
[7]
Watson LM, Bamber E, Schnekenberg RP, et al. Dominant mutations in GRM1 cause spinocerebellar ataxia type 44. Am J Hum Genet 2017; 101: 451-8.
[8]
Nibbeling EAR, Duarri A, Verschuuren-Bemelmans CC, et al. Exome sequencing and network analysis identifies shared mechanisms underlying spinocerebellar ataxia. Brain 2017; 140: 2860-78.
[9]
Gennarino VA, Palmer EE, McDonell LM, et al. A mild PUM1 mutation is associated with adult-onset ataxia, whereas haploinsufficiency causes developmental delay and seizures. Cell 2018; 172: 924-36.
[10]
Rossi M, Perez-Lloret S, Doldan L, et al. Autosomal dominant cerebellar ataxias: A systematic review of clinical features. Eur J Neurol 2014; 21: 607-15.
[11]
Picher-Martel V, Dupre N. Current and promising therapies in autosomal recessive ataxias. CNS Neurol Disord Drug Targets 2018; 17: 161-71.
[12]
Hadjivassiliou M. Advances in therapies of cerebellar disorders: Immune-mediated ataxias. CNS Neurol Disord Drug Targets 2017.
[http://dx.doi.org/10.2174/1871527317666171221110548]
[http://dx.doi.org/10.2174/1871527317666171221110548]
[13]
Keiser MS, Kordasiewicz HB, McBride JL. Gene suppression strategies for dominantly inherited neurodegenerative diseases: Lessons from Huntington’s disease and spinocerebellar ataxia. Hum Mol Genet 2016; 25(1): 53-64.
[14]
Jacobi H, du Montcel ST, Bauer P, et al. Long-term disease progression in spinocerebellar ataxia types 1, 2, 3, and 6: A longitudinal cohort study. Lancet Neurol 2015; 14: 1101-8.
[15]
Seidel K, Siswanto S, Brunt ER, den Dunnen W, Korf HW, Rüb U. Brain pathology of spinocerebellar ataxias. Acta Neuropathol 2012; 124: 1-21.
[16]
Goldfarb LG, Vasconcelos O, Platonov FA, et al. Unstable triplet repeat and phenotypic variability of spinocerebellar ataxia type 1. Ann Neurol 1996; 39: 500-6.
[17]
Ranum LP, Chung MY, Banfi S, et al. Molecular and clinical correlations in spinocerebellar ataxia type I: Evidence for familial effects on the age of onset. Am J Hum Genet 1994; 55: 244-52.
[18]
Klement IA, Skinner PJ, Kaytor MD, Yi H, Hersch SM, Clark HB. Ataxin-1 nuclear localization and aggregation: Role in polyglutamine-induced disease in SCA1 transgenic mice. Cell 1998; 95: 41-53.
[19]
Burright EN, Davidson JD, Duvick LA, Koshy B, Zoghbi HY, Orr HT. Identification of a self-association region within the SCA1 gene product, ataxin-1. Hum Mol Genet 1997; 6: 513-8.
[20]
Mizutani A, Wang L, Rajan H, et al. Boat, an AXH domain protein, suppresses the cytotoxicity of mutant ataxin-1. EMBO J 2005; 24: 3339-51.
[21]
Lam YC, Bowman AB, Jafar-Nejad P, et al. ATAXIN-1 interacts with the repressor Capicua in its native complex to cause SCA1 neuropathology. Cell 2006; 127: 1335-47.
[22]
Yue S, Serra HG, Zoghbi HY, Orr HT, et al. The spinocerebellar ataxia type 1 protein, ataxin1, has RNA-binding activity that is inversely affected by the length of its polyglutamine tract. Hum Mol Genet 2001; 10: 25-30.
[23]
Lim J, Crespo-Barreto J, Jafar-Nejad P, et al. Opposing effects of polyglutamine expansion on native protein complexes contribute to SCA1. Nature 2008; 452: 713-8.
[24]
Emamian ES, Kaytor MD, Duvick LA, et al. Serine 776 of ataxin-1 is critical for polyglutamine-induced disease in SCA1 transgenic mice. Neuron 2003; 38: 375-87.
[25]
Bondar VV, Adamski CJ, Onur TS, et al. PAK1 regulates ATXN1 levels providing an opportunity to modify its toxicity in spinocerebellar ataxia type 1. Hum Mol Genet 2018; 27: 2863-73.
[26]
Xia H, Mao Q, Eliason SL, et al. RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia. Nat Med 2004; 10: 816-20.
[27]
Keiser MS, Geoghegan JC, Boudreau RL, Lennox KA, Davidson BL. RNAi or overexpression: Alternative therapies for Spinocerebellar Ataxia Type 1. Neurobiol Dis 2013; 56: 6-13.
[28]
Keiser MS, Boudreau RL, Davidson BL. Broad therapeutic benefit after RNAi expression vector delivery to deep cerebellar nuclei: Implications for spinocerebellar ataxia type 1 therapy. Mol Ther 2014; 22: 588-95.
[29]
Keiser MS, Kordower JH, Gonzalez-Alegre P, Davidson BL. Broad distribution of ataxin 1 silencing in rhesus cerebella for spinocerebellar ataxia type 1 therapy. Brain 2015; 138: 3555-66.
[30]
Orozco DG, Nodarse FA, Cordovés SR, Auburger G. Autosomal dominant cerebellar ataxia: Clinical analysis of 263 patients from a homogeneous population in Holguín. Cuba Neurology 1990; 40: 1369-75.
[31]
Babovic-Vuksanovic D, Snow K, Patterson MC, Michels VV. Spinocerebellar ataxia type 2 (SCA 2) in an infant with extreme CAG repeat expansion. Am J Med Genet 1998; 79: 383-7.
[32]
Huynh DP, Figueroa K, Hoang N, Pulst SM. Nuclear localization or inclusion body formation of ataxin-2 are not necessary for SCA2 pathogenesis in mouse or human. Nat Genet 2000; 26: 44-50.
[33]
Neuwald AF, Koonin EV. Ataxin2, global regulators of bacterial gene expression and spliceosomal snRNP proteins share a conserved domain. J Mol Med 1998; 76: 3-5.
[34]
Kozlov G, Trempe JF, Khaleghpour K, Kahvejian A, Ekiel I, Gehring K. Structure and function of the Cterminal PABC domain of human poly(A)-binding protein. Proc Natl Acad Sci USA 2001; 98: 4409-13.
[35]
Shibata H, Huynh DP, Pulst SM. A novel protein with RNA-binding motifs interacts with ataxin2. Hum Mol Genet 2000; 9: 1303-13.
[36]
Satterfield TF, Pallanck LJ. Ataxin2 and its Drosophila homolog, ATX2, physically assemble with polyribosomes. Hum Mol Genet 2006; 15: 2523-32.
[37]
Nonhoff U, Ralser M, Welzel F, et al. Ataxin2 interacts with the DEAD/ Hbox RNA helicase DDX6 and interferes with Pbodies and stress granules. Mol Biol Cell 2007; 18: 1385-96.
[38]
Kaehler C, Isensee J, Nonhoff U, et al. Ataxin-2-likeis a regulator of stress granules and processing bodies. PLoS One 2012; 7e50134
[39]
Elden AC, Kim HJ, Hart MP, et al. Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. Nature 2010; 466: 1069-75.
[40]
Scoles DR, Pulst SM. Oligonucleotide therapeutics in neurodegenerative diseases. RNA Biol 2018; 15: 707-14.
[41]
Schöls L, Amoiridis G, Langkafel M, et al. Machado-Joseph disease mutation as the genetic basis of most spinocerebellar ataxias in Germany. J Neurol Neurosurg Psychiatry 1995; 59: 49-50.
[42]
Dürr A, Stevanin G, Cancel G, et al. Spinocerebellar ataxia 3 and Machado-Joseph disease: Clinical, molecular and neuropathological features. Ann Neurol 1996; 39: 490-9.
[43]
Moseley ML, Benzow KA, Schut LJ, et al. Incidence of dominant spinocerebellar and Friedreich triplet repeats among 361 ataxia families. Neurology 1998; 51: 1666-71.
[44]
Watanabe H, Tanaka F, Matsumoto M, et al. Frequency analysis of autosomal dominant cerebellar ataxias in Japanese patients and clinical characterization of spinocerebellar ataxia 6. Clin Genet 1998; 53: 13-9.
[45]
Soong B, Lu Y, Choo K, et al. Frequency analysis of autosomal dominant cerebellar ataxias in Taiwanese patients and clinical and molecular characterization of spinocerebellar ataxia type 6. Arch Neurol 2001; 58: 1105-9.
[46]
Silveira I, Miranda C, Guimarães L, et al. Trinucleotide repeats in 202 families with ataxia: A small expanded (CAG) n allele at the SCA17 locus. Arch Neurol 2002; 59: 623-9.
[47]
Tsai HF, Liu CS, Leu TM, et al. Analysis of trinucleotide repeats in different SCA loci in spinocerebellar ataxia patients and in normal population of Taiwan. Acta Neurol Scand 2004; 109: 355-60.
[48]
Costa Mdo C, Paulson HL. Toward understanding Machado-Joseph disease. Prog Neurobiol 2012; 97: 239-57.
[49]
Burnett B, Li F, Pittman RN. The polyglutamine neurodegenerative protein ataxin-3 binds polyubiquitylated proteins and has ubiquitin protease activity. Hum Mol Genet 2003; 12: 3195-205.
[50]
Schmitt I, Linden M, Khazneh H, et al. Inactivation of the mouse Atxn3 (ataxin-3) gene increases protein ubiquitination. Biochem Biophys Res Commun 2007; 362: 734-9.
[51]
Scaglione KM, Zavodszky E, Todi SV, et al. Ube2w and ataxin-3 coordinately regulate the ubiquitin ligase CHIP. Mol Cell 2011; 43: 599-612.
[52]
Reina CP, Zhong X, Pittman RN. Proteotoxic stress increases nuclear localization of ataxin-3. Hum Mol Genet 2010; 19: 235-49.
[53]
Jana NR, Dikshit P, Goswami A, Kotliarova S, et al. Co-chaperone CHIP associates with expanded polyglutamine protein and promotes their degradation by proteasomes. J Biol Chem 2005; 280: 11635-40.
[54]
Durcan TM, Kontogiannea M, Thorarinsdottir T, et al. The Machado-Joseph disease-associated mutant form of ataxin-3 regulates parkin ubiquitination and stability. Hum Mol Genet 2010; 20: 141-54.
[55]
Alves S, Nascimento-Ferreira I, Auregan G, et al. Allele-specific RNA silencing of mutant ataxin-3 mediates neuroprotection in a rat model of Machado-Joseph disease. PLoS One 2008; 3e3341
[56]
Alves S, Nascimento-Ferreira I, et al. Silencing ataxin-3 mitigates degeneration in a rat model of Machado-Joseph disease: No role for wild-type ataxin-3? Hum Mol Genet 2010; 19: 2380-94.
[57]
Nobrega C, Nascimento-Ferreira I, Onofre I, et al. Silencing mutant ataxin-3 rescues motor deficits and neuropathology in Machado-Joseph disease transgenic mice. PLoS One 2013; 8e52396
[58]
Rodriguez-Lebron E, Costa Mdo C, Luna-Cancalon K, et al. Silencing mutant ATXN3 expression resolves molecular phenotypes in SCA3 transgenic mice. Mol Ther 2013; 21: 1909-18.
[59]
Costa Mdo C, Luna-Cancalon K, Fischer S, et al. Toward RNAi therapy for the polyglutamine disease Machado-Joseph disease. Mol Ther 2013; 21: 1898-908.
[60]
McLoughlin HS, Moore LR, Chopra R, et al. Oligonucleotide therapy mitigates disease in spinocerebellar ataxia type 3 mice. Ann Neurol 2018; 84: 64-77.
[61]
Lin CH, Wu YR, Yang JM, et al. Novel Lactulose and melibiose targeting autophagy to reduce polyq aggregation in cell models of spinocerebellar ataxia 3. CNS Neurol Disord Drug Targets 2016; 15: 351-9.
[62]
Diallo A, Jacobi H, Cook A, et al. Survival in patients with spinocerebellar ataxia types 1, 2, 3, and 6 (EUROSCA): A longitudinal cohort study. Lancet Neurol 2018; 17: 327-34.
[63]
Shizuka M, Watanabe M, Ikeda Y, Mizushima K, Okamoto K, Shoji M. Molecular analysis of a de novo mutation for spinocerebellar ataxia type 6 and (CAG)n repeat units in normal elder controls. J Neurol Sci 1998; 161: 85-7.
[64]
Yabe I, Sasaki H, Matsuura T, et al. SCA6 mutation analysis in a large cohort of the Japanese patients with late-onset pure cerebellar ataxia. J Neurol Sci 1998; 156: 89-95.
[65]
Kordasiewicz HB, Thompson RM, Clark HB, Gomez CM. C-termini of P/Q-type Ca(2+) channel alpha1A subunits translocate to nuclei and promote polyglutamine-mediated toxicity. Hum Mol Genet 2006; 15: 1587-99.
[66]
Du X, Wang J, Zhu H, et al. Second cistron in CACNA1A gene encodes a transcription factor mediating cerebellar development and SCA6. Cell 2013; 154: 118-33.
[67]
Miyazaki Y, Du X, Muramatsu S, Gomez CM. An miRNA- mediated therapy for SCA6 blocks IRES-driven translation of the CACNA1A second cistron. Sci Transl Med 2016; 8: 347-94.
[68]
van de Warrenburg BP, Frenken CW, et al. Striking anticipation in spinocerebellar ataxia type 7: The infantile phenotype. J Neurol 2001; 248: 911-4.
[69]
Aleman TS, Cideciyan AV, Volpe NJ, Stevanin G, Brice A, Jacobson SG. Spinocerebellar ataxia type 7 (SCA7) shows a cone-rod dystrophy phenotype. Exp Eye Res 2002; 74: 737-45.
[70]
Michalik A, Martin JJ, Van Broeckhoven C. Spinocerebellar ataxia type 7 associated with pigmentary retinal dystrophy. Eur J Hum Genet 2004; 12: 2-15.
[71]
Nardacchione A, Orsi L, Brusco A, et al. Definition of the smallest pathological CAG expansion in SCA7. Clin Genet 1999; 56: 232-4.
[72]
Stevanin G, Giunti P, Belal GD, et al. De novo expansion of intermediate alleles in spinocerebellar ataxia 7. Hum Mol Genet 1998; 7: 1809-13.
[73]
Helmlinger D, Hardy S, Eberlin A, et al. Both normal and polyglutamine-expanded ataxin7 are components of TFTC-type GCN5 histone acetyltransferase-containing complexes. Biochem Soc Symp 2006; 73: 155-63.
[74]
Nakamura Y, Tagawa K, Oka T, et al. Ataxin-7 associates with microtubules and stabilizes the cytoskeletal network. Hum Mol Genet 2012; 21: 1099-110.
[75]
Lan X, Koutelou E, Schibler AC, Chen YC, Grant PA, Dent SY. Poly(Q) expansions in ATXN7 affect solubility but not activity of the SAGA deubiquitinating module. Mol Cell Biol 2015; 35: 1777-87.
[76]
Ramachandran PS, Bhattarai S, Singh P, et al. RNA interference-based therapy for spinocerebellar ataxia type 7 retinal degeneration. PLoS One 2014; 9e95362
[77]
Ramachandran PS, Boudreau RL, Schaefer KA, La Spada AR, Davidson BL. Nonallele specific silencing of ataxin-7 improves disease phenotypes in a mouse model of SCA7. Mol Ther 2014; 22: 1635-42.
[78]
Vinton A, Fahey MC, O’Brien TJ, et al. Dentatorubral-pallidoluysian atrophy in three generations, with clinical courses from early asymptomatic elderly to severe juvenile, in an Australian family of Macedonian descent. Am J Med Genet A 2005; 136: 201-4.
[79]
Zádori D, Tánczos T, Jakab K, Vécsei L, Klivényi P. The first identified Central-Eastern European patient with genetically confirmed dentatorubral-pallidoluysian atrophy. Ideggyogy Sz 2015; 68: 68-71.
[81]
Ikeda Y, Shizuka-Ikeda M, Watanabe M, Schmitt M, Okamoto K, Shoji M. Asymptomatic CTG expansion at the SCA8 locus is associated with cerebellar atrophy on MRI. J Neurol Sci 2000; 182: 76-9.
[83]
Zu L, Figueroa KP, Grewal R, Pulst SM. Mapping of a new autosomal dominant spinocerebellar ataxia to chromosome 22. Am J Hum Genet 1999; 64: 594-9.
[84]
Matsuura T, Achari M, Khajavi M, Bachinski LL, Zoghbi HY, Ashizawa T. Mapping of the gene for a novel spinocerebellar ataxia with pure cerebellar signs and epilepsy. Ann Neurol 1999; 45: 407-11.
[85]
Fujigasaki H, Verma IC, Camuzat A, et al. SCA12 is a rare locus for autosomal dominant cerebellar ataxia: A study of an Indian family. Ann Neurol 2001; 49: 117-21.
[86]
Sinha KK, Worth PF, Jha DK, et al. Autosomal dominant cerebellar ataxia: SCA2 is the most frequent mutation in eastern India. J Neurol Neurosurg Psychiatry 2004; 75: 448-52.
[87]
O’Hearn E, Holmes SE, Calvert PC, Ross CA, Margolis RL. SCA-12: Tremor with cerebellar and cortical atrophy is associated with a CAG repeat expansion. Neurology 2001; 56: 299-303.
[88]
O’Hearn E, Holmes SE, Margolis RL. Spinocerebellar ataxia type 12. Handb Clin Neurol 2012; 103: 535-47.
[89]
O’Hearn EE, Hwang HS, Holmes SE, et al. Neuropathology and cellular pathogenesis of spinocerebellar ataxia type 12. Mov Disord 2015; 30: 1813-24.
[90]
Sato N, Amino T, Kobayashi K, et al. Spinocerebellar ataxia type 31 is associated with “inserted” penta-nucleotide repeats containing (TGGAA)n. Am J Hum Genet 2009; 85: 544-57.
[91]
Ikeda Y, Ohta Y, Kobayashi H. Clinical features of SCA36. A novel spinocerebellar ataxia with motor neuron involvement (Asidan). Neurology 2012; 79: 333-41.
[92]
Corral-Juan M, Serrano-Munuera C, Rábano A, Cota-González D, Segarra-Roca A, Ispierto L. Clinical, genetic and neuropathological characterization of spinocerebellar ataxia type 37. Brain 2018; 141: 1981-97.
[93]
Dick KA, Ikeda Y, Day JW, Ranum LP. Spinocerebellar type 5. Handb Clin Neurol 2012; 103: 451-9.
[94]
Schut LJ, Day JW, Clark HB, et al. Spinocerebellar ataxia type 5.
In: T Klockgether, Ed.; Handbook of Ataxia Disorders. Marcel
Dekker: New York 2000; pp. 435-45.
[95]
Liquori C, Schut LJ, Clark HB, et al. Spinocerebellar ataxia type 5
(SCA5). In:M Pandolfo, Ed.; Cerebellar Ataxias. Cambridge University
Press: Cambridge 2002; pp. 445-50.
[96]
Giunti P, Houlden H, Gardner-Thorpe C, et al. Spinocerebellar ataxia type 11. Handb Clin Neurol 2012; 103: 521-34.
[97]
Bauer P, Stevanin G, Beetz C, et al. Spinocerebellar ataxia type 11 (SCA11) is an uncommon cause of dominant ataxia among French and German kindreds. J Neurol Neurosurg Psychiatry 2010; 81: 1229-32.
[98]
Herman-Bert A, Stevanin G, Netter JC, et al. Mapping of spinocerebellar ataxia 13 to chromosome 19q13.3- q13.4 in a family with autosomal dominant cerebellar ataxia and mental retardation. Am J Hum Genet 2000; 67: 229-35.
[99]
Waters MF, Minassian NA, Stevanin G, et al. Mutations in voltage-gated potassium channel KCNC3 cause degenerative and developmental central nervous system phenotypes. Nat Genet 2006; 38: 447-51.
[100]
Montaut S, Apartis E, Chanson JB, et al. SCA13 causes dominantly inherited non-progressive myoclonus ataxia. Parkinsonism Relat Disord 2017; 38: 80-4.
[101]
Duarri A, Nibbeling EA, Fokkens MR, et al. Functional analysis helps to define KCNC3 mutational spectrum in Dutch ataxia cases. PLoS One 2015; 10e0116599
[102]
Khare S, Galeano K, Zhang Y, et al. C-terminal proline deletions in KCNC3 cause delayed channel inactivation and an adult-onset progressive SCA13 with spasticity. Cerebellum 2018; 17: 692-7.
[103]
Chen DH, Raskind WH, Bird TD. Spinocerebellar ataxia type 14. Handb Clin Neurol 2012; 103: 555-9.
[105]
Huin V, Strubi-Vuillaume I, Dujardin K, et al. Expanding the phenotype of SCA19/22: Parkinsonism, cognitive impairment and epilepsy. Parkinsonism Relat Disord 2017; 45: 85-9.
[106]
Seidel K, Küsters B, den Dunnen WF, et al. First patho-anatomical investigation of the brain of a SCA19 patient. Neuropathol Appl Neurobiol 2014; 40: 640-4.
[107]
Delplanque J, Devos D, Huin V, et al. TMEM240 mutations cause spinocerebellar ataxia 21 with mental retardation and severe cognitive impairment. Brain 2014; 137: 2657-63.
[108]
Yahikozawa H, Miyatake S, Sakai T, et al. A japanese family of spinocerebellar ataxia type 21: Clinical and neuropathological studies. Cerebellum 2018; 17: 525-30.
[109]
Zeng S, Zeng J, He M, et al. Spinocerebellar ataxia type 21 exists in the Chinese Han population. Sci Rep 2016; 6: 19897.
[110]
Verbeek DS, van de Warrenburg BP, Wesseling P. Mapping of the SCA23 locus involved in autosomal dominant cerebellar ataxia to chromosome region 20p13-12.3. Brain 2004; 127: 2551-7.
[111]
Jezierska J, Stevanin G, Watanabe H, et al. Identification and characterization of novel PDYN mutations in dominant cerebellar ataxia cases. J Neurol 2013; 260: 1807-12.
[112]
Fawcett K, Mehrabian M, Liu YT, et al. The frequency of spinocerebellar ataxia type 23 in a UK population. J Neurol 2013; 260: 856-9.
[113]
Bakalkin G, Watanabe H, Jezierska J, et al. Prodynorphin mutations cause the neurodegenerative disorder spinocerebellar ataxia type 23. Am J Hum Genet 2010; 87: 593-603.
[114]
Yu GY, Howell MJ, Roller MJ, Xie TD, Gomez CM. Spinocerebellar ataxia type 26 maps to chromosome 19p13.3 adjacent to SCA6. Ann Neurol 2005; 57: 349-54.
[115]
Hekman KE, Yu GY, Brown CD, et al. A conserved eEF2 coding variant in SCA26 leads to loss of translational fidelity and increased susceptibility to proteostatic insult. Hum Mol Genet 2012; 21: 5472-83.
[116]
Brusse E, de Koning I, Maat-Kievit A. Spinocerebellar ataxia associated with a mutation in the fibroblast growth factor 14 gene (SCA27): A new phenotype. Mov Disord 2006; 21: 396-401.
[117]
Szpisjak L, Nemeth VL, Szepfalusi N, et al. Neurocognitive characterization of an SCA28 family caused by a novel AFG3L2 Gene Mutation. Cerebellum 2017; 16: 979-85.
[118]
Cagnoli C, Stevanin G, Brussino A, et al. Missense mutations in the AFG3L2 proteolytic domain account for ∼1.5% of European autosomal dominant cerebellar ataxias. Hum Mutat 2010; 31: 1117-24.
[119]
Zambonin JL, Bellomo A, Ben-Pazi H, Everman DB, Frazer LM, Geraghty MT. Spinocerebellar ataxia type 29 due to mutations in ITPR1: A case series and review of this emerging congenital ataxia. Orphanet J Rare Dis 2017; 12: 121.
[120]
Synofzik M, Helbig KL, Harmuth F, et al. De novo ITPR1 variants are a recurrent cause of early-onset ataxia, acting via loss of channel function. Eur J Hum Genet 2018.
[http://dx.doi.org/10.1038/s41431-018-0206-3]
[http://dx.doi.org/10.1038/s41431-018-0206-3]
[121]
Cadieux-Dion M, Turcotte-Gauthier M, Noreau A, et al. Expanding the clinical phenotype associated with ELOVL4 mutation: Study of a large French-Canadian family with autosomal dominant spinocerebellar ataxia and erythrokeratodermia. JAMA Neurol 2014; 71: 470-5.
[122]
Ozaki K, Doi H, Mitsui J, et al. A novel mutation in ELOVL4 leading to spinocerebellar ataxia (SCA) with the hot cross bun sign but lacking erythrokeratodermia: A broadened spectrum of SCA34. JAMA Neurol 2015; 72: 797-805.
[123]
Guo YC, Lin JJ, Liao YC, Tsai PC, Lee YC, Soong BW. Spinocerebellar ataxia 35: Novel mutations in TGM6 with clinical and genetic characterization. Neurology 2014; 83: 1554-61.
[124]
Tripathy D, Vignoli B, Ramesh N, et al. Mutations in TGM6 induce the unfolded protein response in SCA35. Hum Mol Genet 2017; 26: 3749-62.
[125]
Borroni B, Di Gregorio E, Orsi L, et al. Clinical and neuroradiological features of spinocerebellar ataxia 38 (SCA38). Parkinsonism Relat Disord 2016; 28: 80-6.
[126]
Coutelier M, Blesneac I, Monteil A, et al. A recurrent mutation in cacna1g alters cav3.1 t-type calcium-channel conduction and causes autosomal-dominant cerebellar ataxia. Am J Hum Genet 2015; 97: 726-37.
[127]
Morino H, Matsuda Y, Muguruma K, et al. A mutation in the low voltage-gated calcium channel CACNA1G alters the physiological properties of the channel, causing spinocerebellar ataxia. Mol Brain 2015; 8: 89.
[128]
Li X, Zhou C, Cui L, et al. A case of a novel CACNA1G mutation from a Chinese family with SCA42: A case report and literature review. Medicine (Baltimore) 2018; 97e12148
[129]
Nakamura K, Jeong SY, Uchihara T, et al. SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded polyglutamine in TATA-binding protein. Hum Mol Genet 2001; 10: 1441-8.
[130]
Burke JR, Enghild JJ, Martin ME, et al. Huntingtin and DRPLA proteins selectively interact with the enzyme GAPDH. Nat Med 1996; 2: 347-50.
[131]
García-Murias M, Quintáns B, Arias M, et al. ‘Costa da Morte’ ataxia is spinocerebellar ataxia 36: Clinical and genetic characterization. Brain 2012; 135: 1423-35.
[133]
Lee YC, Durr A, Majczenko K, et al. Mutations in KCND3 cause spinocerebellar ataxia type 22. Ann Neurol 2012; 72: 859-69.
[134]
Yan H, Pablo JL, Pitt GS. FGF14 regulates presynaptic Ca2+ channels and synaptic transmission. Cell Rep 2013; 4: 66-75.
[135]
Di Bella D, Lazzaro F, Brusco A, Plumari M, et al. Mutations in the mitochondrial protease gene AFG3L2 cause dominant hereditary ataxiaSCA28. Nat Genet 2010; 42: 313-21.
[136]
Di Gregorio E, Borroni B, Giorgio E, et al. ELOVL5 mutations cause spinocerebellar ataxia 38. Am J Hum Genet 2014; 95: 209-17.
[137]
Tsoi H, Yu AC, Chen ZS, et al. A novel missense mutation in CCDC88C activates the JNK pathway and causes a dominant form of spinocerebellar ataxia. J Med Genet 2014; 51: 590-5.
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