Details of Disease

General Information of Disease (ID: DISF7WDI)

• Disease Name: Spinocerebellar ataxia type 2
• Synonyms: olivopontocerebellar atrophy Holguin type; spinocerebellar ataxia Cuban type; olivopontocerebellar atrophy, Holguin type; SCA 2; spinocerebellar atrophy 2; spinocerebellar ataxia with slow eye movements; amyotrophic lateral sclerosis, susceptibility to, 13; Wadia-swami syndrome; amyotrophic lateral sclerosis 13; ALS13; cerebellar Degeneration with slow eye movements; olivopontocerebellar atrophy 2; Wadia swami syndrome; spinocerebellar ataxia 2; amyotrophic lateral sclerosis type 13; spinocerebellar Degeneration with slow eye movements; spinocerebellar ataxia, Cuban type; SCA2; ATXN2 autosomal dominant cerebellar ataxia type I; spinocerebellar ataxia type 2; autosomal dominant cerebellar ataxia type I caused by mutation in ATXN2; OPCA2
• Definition: A subtype of type I autosomal dominant cerebellar ataxia (ADCA type I) characterized by truncal ataxia, dysarthria, slowed saccades and less commonly ophthalmoparesis and chorea.
• Disease Hierarchy:
  DISWZ9CJ: Familial amyotrophic lateral sclerosis
  DIS947AF: Autosomal dominant cerebellar ataxia type I
  DIS6BW88: Huntington disease-like syndrome
  DISF7WDI: Spinocerebellar ataxia type 2
• Disease Identifiers:
  MONDO ID: MONDO_0008458
  MESH ID: D020754
  UMLS CUI: C0752121
  OMIM ID: 183090
  MedGen ID: 155704
  Orphanet ID: 98756
  SNOMED CT ID: 715751004

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 10 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CIT	TT3BKTU	Limited	Biomarker	[1]
FOXC1	TTNT3YA	Limited	Biomarker	[2]
GRM1	TTVBPDM	Limited	Biomarker	[3]
ATXN2	TTPQJ7P	Disputed	Biomarker	[4]
ATXN3	TT6A17J	Strong	Biomarker	[5]
CACNA1A	TTX4QDJ	Strong	Biomarker	[6]
PRKCG	TTRFOXJ	Strong	Biomarker	[7]
RGS8	TTWME23	Strong	Biomarker	[8]
TARDBP	TT9RZ03	Strong	Genetic Variation	[9]
ATXN2	TTPQJ7P	Definitive	Autosomal dominant	[10]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
GSTO2	DEHMPZR	Strong	Genetic Variation	[11]

This Disease Is Related to 17 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CIC	OTFXCHNZ	Limited	Biomarker	[12]
GFI1	OT9HB9H8	Limited	Biomarker	[13]
PPP2R2B	OTSFVC82	Limited	Biomarker	[14]
RBM17	OT9ROJCL	Limited	Biomarker	[12]
TTBK2	OT90YSM5	Limited	Biomarker	[15]
AFG3L2	OTRPMAUX	Strong	Biomarker	[16]
ATXN7	OTL3YF1H	Strong	Biomarker	[17]
IGFALS	OTTWCZYM	Strong	Genetic Variation	[18]
JPH3	OTHTJO2I	Strong	Genetic Variation	[19]
LY6E	OTMG16BZ	Strong	Biomarker	[20]
RAI1	OTKLQU00	Strong	Biomarker	[21]
SAR1A	OTSSRVGV	Strong	Biomarker	[22]
SEPTIN3	OTOZ6PIM	Strong	Genetic Variation	[23]
STAU1	OTTR5311	Strong	Biomarker	[24]
TSHZ1	OTYQ9ECW	Strong	Genetic Variation	[25]
ATXN1L	OTYIHGTD	Definitive	Therapeutic	[26]
ATXN2	OT465IGT	Definitive	Autosomal dominant	[10]

References

• [1] Topography of cerebral monoamine transporter availability in families with SCA2 mutations: a voxel-wise [123I]beta-CIT SPECT analysis.Eur J Nucl Med Mol Imaging. 2006 Sep;33(9):1084-90. doi: 10.1007/s00259-006-0104-8. Epub 2006 May 13.
• [2] FOXC1 is required for normal cerebellar development and is a major contributor to chromosome 6p25.3 Dandy-Walker malformation.Nat Genet. 2009 Sep;41(9):1037-42. doi: 10.1038/ng.422. Epub 2009 Aug 9.
• [3] A positive feedback loop linking enhanced mGluR function and basal calcium in spinocerebellar ataxia type 2.Elife. 2017 May 18;6:e26377. doi: 10.7554/eLife.26377.
• [4] Conserved role for Ataxin-2 in mediating endoplasmic reticulum dynamics.Traffic. 2019 Jun;20(6):436-447. doi: 10.1111/tra.12647. Epub 2019 May 8.
• [5] On the distribution of intranuclear and cytoplasmic aggregates in the brainstem of patients with spinocerebellar ataxia type 2 and 3.Brain Pathol. 2017 May;27(3):345-355. doi: 10.1111/bpa.12412. Epub 2016 Aug 2.
• [6] The P/Q-type voltage-dependent calcium channel as pharmacological target in spinocerebellar ataxia type 6: gabapentin and pregabalin may be of therapeutic benefit.Med Hypotheses. 2007;68(1):131-6. doi: 10.1016/j.mehy.2006.06.014. Epub 2006 Aug 8.
• [7] Mutant protein kinase C gamma that causes spinocerebellar ataxia type 14 (SCA14) is selectively degraded by autophagy. Genes Cells. 2010 May;15(5):425-38. doi: 10.1111/j.1365-2443.2010.01395.x. Epub 2010 Apr 11.
• [8] Ataxin-2 regulates RGS8 translation in a new BAC-SCA2 transgenic mouse model.PLoS Genet. 2015 Apr 22;11(4):e1005182. doi: 10.1371/journal.pgen.1005182. eCollection 2015 Apr.
• [9] FTLD-ALS of TDP-43 type and SCA2 in a family with a full ataxin-2 polyglutamine expansion.Acta Neuropathol. 2014 Oct;128(4):597-604. doi: 10.1007/s00401-014-1277-z. Epub 2014 Apr 10.
• [10] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [11] Association of glutathione S-transferase omega polymorphism and spinocerebellar ataxia type 2.J Neurol Sci. 2017 Jan 15;372:324-328. doi: 10.1016/j.jns.2016.11.075. Epub 2016 Dec 5.
• [12] Opposing effects of polyglutamine expansion on native protein complexes contribute to SCA1.Nature. 2008 Apr 10;452(7188):713-8. doi: 10.1038/nature06731. Epub 2008 Mar 12.
• [13] The AXH domain of Ataxin-1 mediates neurodegeneration through its interaction with Gfi-1/Senseless proteins.Cell. 2005 Aug 26;122(4):633-44. doi: 10.1016/j.cell.2005.06.012.
• [14] The spinocerebellar ataxia 12 gene product and protein phosphatase 2A regulatory subunit Bbeta2 antagonizes neuronal survival by promoting mitochondrial fission.J Biol Chem. 2008 Dec 26;283(52):36241-8. doi: 10.1074/jbc.M800989200. Epub 2008 Oct 21.
• [15] Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation, segregate with spinocerebellar ataxia type 11. Nat Genet. 2007 Dec;39(12):1434-6. doi: 10.1038/ng.2007.43. Epub 2007 Nov 25.
• [16] Mutations in the mitochondrial protease gene AFG3L2 cause dominant hereditary ataxia SCA28. Nat Genet. 2010 Apr;42(4):313-21. doi: 10.1038/ng.544. Epub 2010 Mar 7.
• [17] Modulation of the age at onset in spinocerebellar ataxia by CAG tracts in various genes.Brain. 2014 Sep;137(Pt 9):2444-55. doi: 10.1093/brain/awu174. Epub 2014 Jun 26.
• [18] Search for SCA2 blood RNA biomarkers highlights Ataxin-2 as strong modifier of the mitochondrial factor PINK1 levels.Neurobiol Dis. 2016 Dec;96:115-126. doi: 10.1016/j.nbd.2016.09.002. Epub 2016 Sep 3.
• [19] Huntington disease and Huntington disease-like in a case series from Brazil.Clin Genet. 2014 Oct;86(4):373-7. doi: 10.1111/cge.12283. Epub 2013 Oct 17.
• [20] Long-Term Suppression of Disabling Tremor by Thalamic Stimulation in a Patient with Spinocerebellar Ataxia Type 2.Stereotact Funct Neurosurg. 2019;97(4):241-243. doi: 10.1159/000504062. Epub 2019 Nov 19.
• [21] Modulation of age at onset in Huntington's disease and spinocerebellar ataxia type 2 patients originated from eastern India.Neurosci Lett. 2003 Jul 17;345(2):93-6. doi: 10.1016/s0304-3940(03)00436-1.
• [22] NESSCA Validation and Responsiveness of Several Rating Scales in Spinocerebellar Ataxia Type 2.Cerebellum. 2017 Aug;16(4):852-858. doi: 10.1007/s12311-017-0855-8.
• [23] Progression of early features of spinocerebellar ataxia type 2 in individuals at risk: a longitudinal study.Lancet Neurol. 2014 May;13(5):482-9. doi: 10.1016/S1474-4422(14)70027-4. Epub 2014 Mar 20.
• [24] Staufen1 links RNA stress granules and autophagy in a model of neurodegeneration.Nat Commun. 2018 Sep 7;9(1):3648. doi: 10.1038/s41467-018-06041-3.
• [25] Common origin of pure and interrupted repeat expansions in spinocerebellar ataxia type 2 (SCA2).Am J Med Genet B Neuropsychiatr Genet. 2010 Mar 5;153B(2):524-531. doi: 10.1002/ajmg.b.31013.
• [26] Duplication of Atxn1l suppresses SCA1 neuropathology by decreasing incorporation of polyglutamine-expanded ataxin-1 into native complexes. Nat Genet. 2007 Mar;39(3):373-9. doi: 10.1038/ng1977. Epub 2007 Feb 18.