UBQLN2 mutation causing heterogeneous X-linked dominant neurodegeneration

Academic Article


  • We report a 5-generation family with phenotypically diverse neurodegenerative disease including relentlessly progressive choreoathetoid movements, dysarthria, dysphagia, spastic paralysis, and behavioral dementia in descendants of a 67-year-old woman with amyotrophic lateral sclerosis. Disease onset varied with gender, occurring in male children and adult women. Exome sequence analyses revealed a novel mutation (c.1490C>T, p.P497L) in the ubiquilin-2 gene (UBQLN2) with X-linked inheritance in all studied affected individuals. As ubiquilin-2-positive inclusions were identified in brain, we suggest that mutant peptide predisposes to protein misfolding and accumulation. Our findings expand the spectrum of neurodegenerative phenotypes caused by UBQLN2 mutations. © 2014 American Neurological Association.
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    Digital Object Identifier (doi)

    Author List

  • Fahed AC; McDonough B; Gouvion CM; Newell KL; Dure LS; Bebin M; Bick AG; Seidman JG; Harter DH; Seidman CE
  • Start Page

  • 793
  • End Page

  • 798
  • Volume

  • 75
  • Issue

  • 5