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General Information
Name
spinocerebellar ataxia 10
FlyBase ID
FBhh0000133
Overview

This report describes spinocerebellar ataxia 10 (SCA10), which is a subtype of spinocerebellar ataxia; SCA10 is inherited as an autosomal dominant. SCA10 is one of a number spinocerebellar ataxias caused by expansion of trinucleotide repeats within the coding -- or noncoding -- region of the causative gene. The human gene implicated in this disease is ATXN10, which encodes ataxin 10, a protein of unknown function. There is one high-scoring fly ortholog, CG4975, for which RNAi targeting constructs have been generated.

SCA10 is associated with an extremely large expansion of a pentanucleotide repeat within an intron of ATXN10; hundreds to thousands of copies of the repeat have been observed in individuals diagnosed with SCA10. The number of this pentanucleotide repeat typically ranges from 9 to 32; intermediate alleles (280 to 850 repeats) may show reduced penetrance.

A transgenic construct of the human gene Hsap\ATXN10 has been introduced into flies; this construct consists of an expansion of the pentanucleotide repeat associated with SCA10 (65 copies of the repeat). When expressed in the developing eye, the Hsap\ATXN10 transcript with the repeat expansion fails to induce any phenotypic abnormalities. Candidate modifier genes were identified by microarray experiments assessing transcriptional effects of pan-neuronal expression of the repeat-expansion transcript. Overexpression of one of these genes (sgg) in the eye in combination with the Hsap\ATXN10 transcript with the repeat expansion results in a neurodegenerative phenotype.

Variant(s) implicated in human disease tested (as transgenic human gene, ATXN10): ATXN10, (ATTCT)n EXPANSION in a modified transcript.

The fly gene orthologous to ATXN10, CG4975, has not been characterized genetically. One physical interaction is reported; see below and in the gene report for CG4975.

To investigate general mechanisms of RNA repeat diseases, work has been done in flies using UAS constructs to drive synthetic constructs of nucleotide repeats of variable composition and length; see FBhh0000059.

[updated Aug. 2019 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: spinocerebellar ataxia, autosomal dominant
Symptoms and phenotype

The autosomal dominant cerebellar degenerative disorders are generally referred to as 'spinocerebellar ataxias,' (SCAs) even though 'spinocerebellar' is a hybrid term, referring to both clinical signs and neuroanatomical regions (Margolis, 2003, pubmed:14628900). Neuropathologists have defined SCAs as cerebellar ataxias with variable involvement of the brainstem and spinal cord, and the clinical features of the disorders are caused by degeneration of the cerebellum and its afferent and efferent connections, which involve the brainstem and spinal cord (Schols et al., 2004 pubmed:15099544; Taroni and DiDonato, 2004, pubmed:15263894). [From OMIM:164400, 2015.10.27]

The autosomal dominant cerebellar degenerative disorders are generally referred to as 'spinocerebellar ataxias' (SCAs). Neuropathologists have defined SCAs as cerebellar ataxias with variable involvement of the brainstem and spinal cord; the clinical features of the disorders are caused by degeneration of the cerebellum and its afferent and efferent connections, which involve the brainstem and spinal cord (Schols et al., 2004 pubmed:15099544; Taroni and DiDonato, 2004, pubmed:15263894). [From OMIM:164400, 2015.10.27]

Specific Disease Summary: spinocerebellar ataxia 10
OMIM report

[SPINOCEREBELLAR ATAXIA 10; SCA10](https://omim.org/entry/603516)

Human gene(s) implicated

[ATAXIN 10; ATXN10](https://omim.org/entry/611150)

Symptoms and phenotype

SCA10 is characterized by slowly progressive cerebellar ataxia that usually starts as poor balance and unsteady gait, followed by upper-limb ataxia, scanning dysarthria, and dysphagia. The disease is exclusively found in Latin American populations, particularly those with Amerindian admixture. Abnormal tracking eye movements are common. Recurrent seizures after the onset of gait ataxia have been reported with variable frequencies among different families. Some individuals have cognitive dysfunction, behavioral disturbances, mood disorders, mild pyramidal signs, and peripheral neuropathy. Onset ranges from age 12 to 48 years. [from GeneReviews, Spinocerebellar Ataxia Type 10, pubmed:20301354 2016.01.21]

Genetics

Spinocerebellar ataxia 10 (SCA10) is caused by an expanded 5-bp repeat (ATTCT) in intron 9 of the ATXN10 gene. Normal alleles have 10 to 29 repeats, and pathologic alleles usually have 400 to 4,500 repeats, although a single patient with 280 repeats has been reported (Matsuura et al., 2004, pubmed:15127363; Alonso et al., 2006, pubmed:16717236). [From OMIM:603516, 2016.01.20]

Expansion of an ATTCT repeat from 9-32 copies to 800-4500 copies in an intronic region of this locus has been associated with spinocerebellar ataxia, type 10. [NCBI Gene, ATXN10; 2019.08.15]

Intermediate alleles (280 to 850 repeats) may show reduced penetrance. [Gene Reviews, Spinocerebellar Ataxia Type 10; 2019.08.15]

Cellular phenotype and pathology
Molecular information

ATXN10 is necessary for the survival of cerebellar neurons. It induces neuritogenesis by activating the Ras-MAP kinase pathway. It may play a role in the maintenance of a critical intracellular glycosylation level and homeostasis. [From UniProt, uniprot:Q9UBB4 2016.01.21]

External links
Disease synonyms
SCA10
spinocerebellar ataxia 10; SCA10
spinocerebellar ataxia type 10
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
Symbol / Name
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

One to one: 1 human to 1 Drosophila.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (0)
    Synthetic Gene(s) Used (0)
    Summary of Physical Interactions (0 groups)
    Alleles Reported to Model Human Disease (Disease Ontology) (1 alleles)
    Models Based on Experimental Evidence ( 1 )
    Modifiers Based on Experimental Evidence ( 0 )
    Allele
    Disease
    Interaction
    References
    Genetic Tools, Stocks and Reagents
    Sources of Stocks
    Contact lab of origin for a reagent not available from a public stock center.
    Bloomington Stock Center Disease Page
    Selected mammalian transgenes
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    Publicly Available Stocks
    Selected Drosophila transgenes
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    Publicly Available Stocks
    RNAi constructs available
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    Publicly Available Stocks
    Selected Drosophila classical alleles
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    Publicly Available Stocks
    References (7)