Mitochondrial complex I NUBPL mutations cause combined dystonia with bilateral striatal necrosis and cerebellar atrophy

B. Balint*, G. Charlesworth, M. Stamelou, L. Carr, N. E. Mencacci, N. W. Wood, K. P. Bhatia

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Background and purpose: The recent advances in genetics have helped to unravel the cause of many dystonia syndromes. With the broadening spectrum of genetically defined dystonia syndromes, distinct clinico-radiological phenotypes are a welcome handle to guide the diagnostic work-up. Methods: Exome sequencing was used to elucidate the genetic cause of a syndrome characterized by generalized dystonia, pyramidal and cerebellar involvement, with bilateral striatal necrosis (BSN) and cerebellar atrophy on magnetic resonance imaging. Homozygosity mapping and linkage analysis were used in a supportive role. Known genetic causes of BSN were excluded by use of exome data or Sanger sequencing. Results: Compound heterozygous mutations were identified in the NUBPL gene in a small UK kindred. The gene lay in a region of positive linkage and segregated with disease in a family of six individuals. Conclusion: NUBPL mutations cause early onset, autosomal recessive generalized dystonia with cerebellar ataxia, pyramidal signs, preserved cognition and a distinct magnetic resonance imaging appearance with BSN and cerebellar atrophy.

Original languageEnglish (US)
Pages (from-to)1240-1243
Number of pages4
JournalEuropean Journal of Neurology
Volume26
Issue number9
DOIs
StatePublished - 2019

Keywords

  • NUBPL
  • ataxia
  • autosomal recessive
  • bilateral striatal necrosis
  • dystonia

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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