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CAPN1 mutations broadening the hereditary spastic paraplegia/spinocerebellar ataxia phenotype
  1. Jeffrey Lambe,
  2. Bernadette Monaghan,
  3. Tudor Munteanu,
  4. Janice Redmond
  1. Department of Neurology, St James’s Hospital, Dublin, Ireland
  1. Correspondence to Dr Jeffrey Lambe, Department of Neurology, St James’s Hospital, Dublin 8, Ireland; jeffrey.lambe{at}ucdconnect.ie

Abstract

Increasing availability of next-generation sequencing technologies has revealed several limitations of diagnosis-driven traditional clinicogenetic disease classifications, particularly among patients with an atypical or mixed phenotype. Hereditary spastic paraplegia (HSP) and spinocerebellar ataxia (SCA) are two such disease entities with an often overlapping presentation, in which next generation exome sequencing has played a key role in identification of genes causing disease along a continuum of ataxia and spasticity. We describe a patient who presented with features of both ataxia and spasticity, in whom initial diagnostic testing was inconclusive. Ultimately next generation exome sequencing identified homozygosity for a pathogenic variant in exon 13 of the CAPN1 gene c.1534C>T(p.Arg512Cys). This case supports consideration of a less discriminatory classification system among such patients, potentially allowing for more expedient diagnosis through testing of a larger gene panel along the ‘ataxia-spasticity spectrum’.

  • cerebellar ataxia
  • genetics
  • heredit spastic paraplegia

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Footnotes

  • Contributors All authors contributed equally to this study.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Ethical approval was granted by St. James’s and Adelaide and Meath Hospital’s Research and Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed by Henry Houlden, London, UK.

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