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Genetics

Utility of next-generation sequencing in ataxias

Nature Reviews Neurology volume 9, pages 614–615 (2013)Cite this article

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New research indicates that next-generation sequencing (NGS) can improve the diagnostic yield in a highly selected group of patients with ataxia, following comprehensive exclusion work-up of other causes. However, routine practical application of NGS will depend on refinement of current technologies to facilitate data interpretation, and cost-effectiveness analysis in different patient groups.

Ataxia is a nonspecific neurological sign frequently associated with cerebellar dysfunction, although it can also involve vestibular and sensory systems. Patients with ataxia have a tendency to fall owing to poor coordination. The term spinocerebellar ataxia (SCA) is commonly used if the ataxia is attributable to dysfunction of both the cerebellum and the spinal cord.1,2 For the past 20 years, the identification of numerous causative mutations for the hereditary forms of ataxias have modified the practice of clinical neurology, which historically has prided itself on the unravelling of 'iconic' clinical syndromes. The discovery that SCA type 3 (SCA3) is allelic to Machado–Joseph Disease (which was initially reported among Portuguese emigrants from the Azorean islands) is a good illustration of how a genetic discovery unites the various clinical phenotypes, eventually translating into an improved clinical diagnostic paradigm.2,3,4 However, inherited ataxias remain a diagnostic challenge because of their clinical heterogeneity, and the fact that they are frequently accompanied by a wide spectrum of other neurological symptoms and signs. Individual ataxia-associated genes can be affected by a myriad of mutations, and can be linked to a variety of different neurological diseases.2,4 More than 40 genes and loci have been identified for the autosomal dominant and recessive forms of SCA alone.2,3

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Acknowledgements

The author acknowledges support from the National Medical Research Council, Singapore Millennium Foundation and Duke-NUS Graduate Medical School.

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  1. Department of Neurology, National Neuroscience Institute, Duke-NUS Graduate Medical School, Outram Road, The Academia, Level 4, 169608, Singapore

    Eng-King Tan

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Tan, EK. Utility of next-generation sequencing in ataxias. Nat Rev Neurol 9, 614–615 (2013). https://doi.org/10.1038/nrneurol.2013.212

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