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Genetics of the Autosomal Dominant Spinocerebellar Ataxias

  1. Marc Corral-Juan1,
  2. Jordi Corral2,
  3. Héctor San Nicolás2,
  4. Victor Volpini2,
  5. Antoni Matilla-Dueñas1

Published Online: 17 OCT 2011

DOI: 10.1002/9780470015902.a0006076

eLS

eLS

How to Cite

Corral-Juan, M., Corral, J., San Nicolás, H., Volpini, V. and Matilla-Dueñas, A. 2011. Genetics of the Autosomal Dominant Spinocerebellar Ataxias. eLS. .

Author Information

  1. 1

    Universitat Autònoma de Barcelona, Basic, Translational and Molecular Neurogenetics Research Unit in Neurodegenerative Diseases, Department of Neurosciences, Health Sciences Research Institute Germans Trias i Pujol (IGTP), Badalona, Barcelona, Spain

  2. 2

    Institut d'Investigacions Biomèdiques de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Molecular Diagnosis Center of Inherited Diseases, Barcelona, Spain

Publication History

  1. Published Online: 17 OCT 2011

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 noncerebellar symptoms that, in many cases, defy differentiation based on clinical characterisation alone. The clinical symptoms are triggered by neurodegeneration of the cerebellum and its rely connections. Currently, there are 43 different genes associated with the autosomal dominant SCAs identified. Genetic studies refine the clinical diagnosis, provide molecular testing of at risk, a/presymptomatic, prenatal or preimplantation and facilitate genetic counselling in 27 SCA subtypes. Recent scientific advances are shedding light into the altered molecular pathways involved and the mechanisms by which the mutant gene products underlie neurodegeneration. This knowledge should be translated into effectively developing selective therapeutic strategies. The scope of this chapter is to provide an updated summary of the genetic aspects of the autosomal dominant SCAs.

Key Concepts:

  • Ataxia, a term that derives from the Greek, is a neurological disorder characterised by loss of control of voluntary body movements.

  • Spinocerebellar ataxias, also known as SCAs, are a highly heterogeneous group of neurodegenerative diseases caused by cerebellar atrophy triggered by predominant loss of Purkinje cells in the cerebellum.

  • The term ‘spinocerebellar ataxias’ is commonly used for those inherited progressive, congenital or episodic ataxias presenting an autosomal dominant inheritance.

  • Mutations presenting incomplete penetrance in at least 43 genes are responsible for ataxia in the autosomal dominant SCAs.

  • CAG repeat expansions encoding for polyglutamines in the gene products currently underlie neurodegeneration in seven spinocerebellar ataxia subtypes.

  • Anticipation is a genetic phenomenon whereby the clinical symptoms become apparent at an earlier age as it is passed on to the next generation. This is associated with the germline transmission of an unstable expanded CAG-triplet repeat.

Keywords:

  • spinocerebellar ataxias;
  • cerebellum;
  • neurodegeneration;
  • movement disorders;
  • Purkinje cells;
  • polyglutamine expansions;
  • molecular diagnosis;
  • genetic counselling;
  • ataxia scales