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The Ever Expanding Spinocerebellar Ataxias. Editorial

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Abstract

The spinocerebellar ataxias (SCAs) are a clinically, genetically, and neuropathologically heterogeneous group of neurological disorders defined by variable degrees of cerebellar ataxia often accompanied by additional cerebellar and non-cerebellar symptoms that, in many cases, defy differentiation based on clinical characterisation alone. The clinical symptoms are triggered by neurodegeneration of the cerebellum and its relay connexions. The current identification of at least 43 SCA subtypes and the causative molecular defects in 27 of them refine the clinical diagnosis, provide molecular testing of at risk, a/pre-symptomatic, prenatal or pre-implantation and facilitate genetic counselling. The recent discovery of new causative SCA genes along with the respective scientific advances is uncovering high complexity and altered molecular pathways involved in the mechanisms by which the mutant gene products cause pathogenesis. Fortunately, the intensive ongoing clinical and neurogenetic research together with the applied molecular approaches is sure to yield scientific advances that will be translated into developing effective treatments for the spinocerebellar ataxias and other similar neurological conditions.

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Abbreviations

ADCA:

Autosomal dominant spinocerebellar ataxia

ADHD:

Attention deficit/hyperactivity disorder

ADNOA:

Ataxia with deafness, narcolepsy, and optic atrophy

ADSA:

Autosomal dominant sensory ataxia

AFG3L2:

ATPase family gene 3-like 2

ARP1:

Actin-related protein-1

ATN1:

Atrophin-1

ATXN1:

Ataxin-1

ATXN2:

Ataxin-2

ATXN3:

Ataxin-3

ATXN8:

Ataxin-8

ATXN8OS:

Ataxin-8 opposite strand

Ca2+ :

Calcium ion

BEAN1:

Brain expressed associated NEDD4

CACNA1A:

Calcium channel, voltage-dependent, P/Q type, alpha 1A subunit

CACNB4:

Calcium channel, voltage-dependent, subunit beta 4

CAG:

DNA sequence coding for glutamine

DRPLA:

Dentatorubral-pallidoluysian atrophy

EA:

Episodic ataxia

EAAT1:

Excitatory amino acid transporter 1

EMQN:

European Molecular Quality Genetics network

FGF14:

Fibroblast growth factor 14

HGNC:

HUGO Gene Nomenclature Committee

IFRD1:

Interferon-related developmental regulator gene 1

INAS:

Inventory of non-ataxia symptoms

ITPR:

Inositol triphosphate receptor

K+ :

Potassium ion

KCNA1:

Potassium voltage-gated channel, shaker-related subfamily, member 1

KCNC3:

Potassium voltage-gated channel subfamily C member 3

MJD:

Machado–Joseph disease

NOP56:

Ribonucleoprotein homolog yeast

OECD:

Organisation for Economic Co-operation and Development

PDYN:

Prodynorphin

PPP2R2B:

Serine/threonine protein phosphatase 2 (formerly 2A) 55 kDa regulatory subunit B beta isoform

PRKCG:

Protein kinase C gamma

SARA:

Scale for the Assessment and Rating of Ataxia

SCA:

Spinocerebellar ataxia

SCN8A:

Sodium channel, voltage gated, type VIII, alpha subunit

SLC1A3:

Solute carrier family 1 member 3

SPAX1:

Autosomal dominant spastic ataxia

SPTBN2:

Beta-III spectrin

TBP:

TATA box binding protein

TK2:

Thymidine kinase 2

TTBK2:

Tau tubulin kinase-2

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    Google Scholar 

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Acknowledgments

Dr. Ivelisse Sanchez’s helpful comments and suggestions are kindly acknowledged. Dr. Antoni Matilla’s scientific research on ataxias is funded by the Spanish Ministry of Science and Innovation (BFU2008-00527/BMC), the Carlos III Health Institute (CP08/00027), the Latin American Science and Technology Development Programme (CYTED) (RIBERMOV, 210RT0390), the European Commission (EUROSCA project, LHSM-CT-2004-503304), and the Fundació de la Marató de TV3 (Televisió de Catalunya, 100730). We are indebted to the Spanish Ataxia Association (FEDAES), the Spanish Federation for Rare Diseases (FEDER), and the ataxia patients for their continuous support and motivation. Antoni Matilla is a Miguel Servet Investigator in Neurosciences of the Spanish National Health System.

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None declared.

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Authors and Affiliations

  1. Basic, Translational and Molecular Neurogenetics Research Unit in Neurodegenerative Diseases, Department of Neurosciences, Health Sciences Research Institute Germans Trias i Pujol (IGTP), Universitat Autònoma de Barcelona, Ctra. de Can Ruti, Camí de les escoles s/n, 08916, Badalona, Barcelona, Spain

    Antoni Matilla-Dueñas

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Correspondence to Antoni Matilla-Dueñas.

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Matilla-Dueñas, A. The Ever Expanding Spinocerebellar Ataxias. Editorial. Cerebellum 11, 821–827 (2012). https://doi.org/10.1007/s12311-012-0376-4

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