TITLE:
Parkin and LRRK2/Dardarin Mutations in Early Onset Parkinson’s Disease in the Basque Country (Spain)
AUTHORS:
J. F. Martí Massó, J. Ruiz-Martínez, C. Paisán-Ruiz, A. Gorostidi, A. Bergareche, A. Lopez de Munain, A. Alzualde, J. Pérez-Tur
KEYWORDS:
Parkin, Early Onset Parkinsonism, Parkinson’s Disease, LRRK2, Dardarin
JOURNAL NAME:
Journal of Behavioral and Brain Science,
Vol.5 No.3,
March
11,
2015
ABSTRACT: 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).