The authors report no conflict of interest.
Recurrent mutations in DNAJC5 cause autosomal dominant Kufs disease
Article first published online: 7 NOV 2012
© 2012 John Wiley & Sons A/S
Volume 83, Issue 6, pages 571–575, June 2013
How to Cite
Recurrent mutations in DNAJC5 cause autosomal dominant Kufs disease., , , , , , , , , , , , , .
- Issue published online: 23 APR 2013
- Article first published online: 7 NOV 2012
- Accepted manuscript online: 14 SEP 2012 08:57AM EST
- Manuscript Revised: 12 SEP 2012
- Manuscript Accepted: 12 SEP 2012
- Manuscript Received: 18 JUL 2012
- La Fondation GO
- Le Fond de la Recherche en Santé du Québec
- National Health and Medical Research Council
- exome sequencing;
- neurodegenerative disorders;
- neuronal ceroid lipofuscinosis
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.