The inherited ataxias: genetic heterogeneity, mutation databases, and future directions in research and clinical diagnostics

Hum Mutat. 2012 Sep;33(9):1324-32. doi: 10.1002/humu.22132. Epub 2012 Jul 2.


The inherited cerebellar ataxias are a diverse group of clinically and genetically heterogeneous neurodegenerative disorders. Inheritance patterns of these disorders can be complex with autosomal dominant, autosomal recessive, X-linked, and mitochondrial inheritance demonstrated by one or more ataxic syndromes. The broad range of mutation types found in inherited ataxia contributes to the complex genetic etiology of these disorders. The majority of inherited ataxias are caused by repeat expansions; however, conventional mutations are important causes of the rarer dominant and recessive ataxias. Advances in sequencing technology have allowed for much broader testing of these rare ataxia genes. This is relevant to the aims of the Human Variome Project, which aims to collate and store gene variation data through mutation databases. Variant data is currently located in a range of public and commercial resources. Few locus-specific databases have been created to catalogue variation in the dominant ataxia genes although there are several databases for some recessive genes. Developing these resources will facilitate a better understanding of the complex genotype-phenotype relationships in these disorders and assist interpretation of gene variants as testing for rarer ataxia genes becomes commonplace.

Publication types

  • Review

MeSH terms

  • Databases, Genetic*
  • Genes, Recessive
  • Genetic Association Studies
  • Genetic Heterogeneity*
  • Genetic Loci
  • Genetic Research
  • Genome, Human
  • Humans
  • Microsatellite Repeats
  • Mutation*
  • Spinocerebellar Degenerations / diagnosis*
  • Spinocerebellar Degenerations / genetics*