Author(s)

J. F. Martí Massó^1,2,3,4*, J. Ruiz-Martínez^1,2,3, C. Paisán-Ruiz⁵, A. Gorostidi^2,3, A. Bergareche^1,2,3, A. Lopez de Munain^1,2,3,4, A. Alzualde³, J. Pérez-Tur^2,6

¹Servicio Neurologia, Hospital Donostia, San Sebastián, Spain.
²Center for Biomedical Research in Neurodegenerative Diseases Network (CIBERNED), Spain.
³Neurosciences Area, Biodonostia Institute, San Sebastián, Spain.
⁴Department of Neuroscience, University of Basque Country, UPV-EHU, San Sebastián, Spain.
⁵Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA.
⁶Molecular Genetics Unit, Instituto de Biomedicina de Valencia-CSIC, Valencia, Spain.

We have performed a complete screening of the Parkin gene (PRKN2) and looked for p.Gly2019Ser (G2019S) and p.Arg1441Gly (R1441G) LRRK2/dardarin gene mutations in twenty seven patients with Parkinson’s disease (PD) with an age at onset younger than 50 years (EOPD), living in Gipuzkoa (Basque Country, Spain). Thirteen of them (48%) were PRKN2 mutation carriers. The c.255-256DelA mutation was the most frequent, followed by a deletion involving exons 3 and 4. A deletion involving exons 3 and 12 of the PRKN2 gene and R1441G LRRK2 mutation was found together in one PD patient. Four out of fourteen PRKN2 negative patients carried the p.G2019S mutation. Both PRKN2 mutation carriers and non-carriers presented frequently with family history (10 PRKN2 mutation carriers and 8 PRKN2 non-carriers); in fact, five patients without a known gene mutation had a first degree relative affected, suggesting another monogenic disease. PRKN2 carriers presented with a younger age at onset (36.7 vs. 41.7) and more benign disease progression. Indeed, those PD patients younger than forty who initially presented with unilateral tremor became shortly bilateral. Relatively, symmetric parkinsonism and slow disease progression carried more frequently PRKN2 mutations than patients with unilateral akinetic rigid parkinsonism and age at onset later than 40 years. As expected in a recessive disease, PRKN2 patients present more often with affected siblings and unaffected patients. The G2019S LRRK2 mutation, less prevalent than R1441G in our area, may be also a frequent cause of PD in EOPD (4 patients).

Parkin, Early Onset Parkinsonism, Parkinson’s Disease, LRRK2, Dardarin

Massó, J. , Ruiz-Martínez, J. , Paisán-Ruiz, C. , Gorostidi, A. , Bergareche, A. , de Munain, A. , Alzualde, A. and Pérez-Tur, J. (2015) Parkin and LRRK2/Dardarin Mutations in Early Onset Parkinson’s Disease in the Basque Country (Spain). Journal of Behavioral and Brain Science, 5, 101-108. doi: 10.4236/jbbs.2015.53010.