Abstract |
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 (CSPĪ±), 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.
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Authors | M Cadieux-Dion, E Andermann, P Lachance-Touchette, O Ansorge, C Meloche, A Barnabé, R I Kuzniecky, F Andermann, E Faught, S Leonberg, J A Damiano, S F Berkovic, G A Rouleau, P Cossette |
Journal | Clinical genetics
(Clin Genet)
Vol. 83
Issue 6
Pg. 571-5
(Jun 2013)
ISSN: 1399-0004 [Electronic] Denmark |
PMID | 22978711
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2012 John Wiley & Sons A/S. |
Chemical References |
- HSP40 Heat-Shock Proteins
- Membrane Proteins
- cysteine string protein
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Topics |
- 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, genetics, pathology)
- Pedigree
- Polymorphism, Genetic
- Sequence Deletion
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