Recurrent mutations in DNAJC5 cause autosomal dominant Kufs disease

Clin Genet. 2013 Jun;83(6):571-5. doi: 10.1111/cge.12020. Epub 2012 Nov 7.


We sought to identify the molecular basis of the autosomal dominant form of Kufs disease, an adult onset form of neuronal ceroid lipofuscinosis. We used a combination of classic linkage analysis and Next Generation Sequencing to map and identify mutations in DNAJC5 in a total of three families. We analyzed the clinical manifestations in 20 individuals with mutation in DNAJC5. We report here the mapping and the identification of a p.L116del mutation in DNAJC5 segregating with the disease in two distinct American families, as well as a p.L115R mutation in an additional family. The age of onset and clinical manifestations were very homogeneous among mutation positive individuals, including generalized tonic-clonic seizures, myoclonus, ataxia, speech deterioration, dementia, and premature death. A few individuals also exhibited parkinsonism. DNAJC5, which encodes the cysteine string protein (CSPα), a presynaptic protein implicated in neurodegeneration, causes autosomal dominant Kufs disease. The leucine residues at positions 115 and 116 are hotspots for mutations and result in a homogeneous phenotype of progressive myoclonus epilepsy with onset around 30 years old.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Amino Acid Sequence
  • Base Sequence
  • DNA Mutational Analysis
  • Family Health
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • HSP40 Heat-Shock Proteins / genetics*
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Mutation*
  • Neuronal Ceroid-Lipofuscinoses / epidemiology
  • Neuronal Ceroid-Lipofuscinoses / genetics*
  • Neuronal Ceroid-Lipofuscinoses / pathology
  • Pedigree
  • Polymorphism, Genetic
  • Sequence Deletion


  • HSP40 Heat-Shock Proteins
  • Membrane Proteins
  • cysteine string protein