Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease

Topic: Brain proteins, microglia and lab models

Parkinson's disease (PD; OMIM #168600) is the second most common neurodegenerative disorder in the Western world and presents as a progressive movement disorder. The hallmark pathological features of PD are loss of dopaminergic neurons from the substantia nigra and neuronal intracellular Lewy body inclusions. Parkinsonism is typically sporadic in nature; however, several rare familial forms are linked to genetic loci, and the identification of causal mutations has provided insight into the disease process. PARK8, identified in 2002 by Funayama and colleagues, appears to be a common cause of familial PD. We describe here the cloning of a novel gene that contains missense mutations segregating with PARK8-linked PD in five families from England and Spain. Because of the tremor observed in PD and because a number of the families are of Basque descent, we have named this protein dardarin, derived from the Basque word dardara, meaning tremor.

Key findings

• The hallmark pathological features of PD are loss of dopaminergic neurons from the substantia nigra and neuronal intracellular Lewy body inclusions.
• Parkinsonism is typically sporadic in nature; however, several rare familial forms are linked to genetic loci, and the identification of causal mutations has provided insight into the disease process.
• PARK8, identified in 2002 by Funayama and colleagues, appears to be a common cause of familial PD.
• We describe here the cloning of a novel gene that contains missense mutations segregating with PARK8-linked PD in five families from England and Spain.
• Because of the tremor observed in PD and because a number of the families are of Basque descent, we have named this protein dardarin, derived from the Basque word dardara, meaning tremor.

Why it matters

This study cloned a novel gene containing missense mutations that segregate with PARK8-linked Parkinson's disease in five families, naming the protein dardarin. It concerns the genetics of familial Parkinson's disease, not treating, curing or preventing Alzheimer's disease.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1016/j.neuron.2004.10.023
• PubMed: 15541308
• Original source →
• Free full text: Neuron →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

@article{paisanruiz2004-15541308,
  author  = {Paisán-Ruíz, C. and Jain, S. and Evans, E. W. and Gilks, W. P. and Simón, J. and van der Brug, M. and López de Munain, A. and Aparicio, S. and others},
  title   = {{Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease}},
  journal = {Neuron},
  year    = {2004},
  doi     = {10.1016/j.neuron.2004.10.023},
  pmid    = {15541308},
  url     = {https://doi.org/10.1016/j.neuron.2004.10.023}
}

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease Nature · 1995-06-01 · usefulness score 64/100 · Genetics

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