Parkin and <i>LRRK2</i>/Dardarin Mutations in Early Onset Parkinson’s Disease in the Basque Country (Spain)

Abstract

We have performed a complete screening of the Parkin gene ( PRKN 2) and looked for p.Gly2019Ser (G2019S) and p.Arg1441Gly (R1441G) LRRK 2/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 PRKN 2 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 PRKN 2 gene and R1441G LRRK 2 mutation was found together in one PD patient. Four out of fourteen PRKN 2 negative patients carried the p.G2019S mutation. Both PRKN 2 mutation carriers and non-carriers presented frequently with family history (10 PRK N 2 mutation carriers and 8 PRKN 2 non-carriers); in fact, five patients without a known gene muta tion had a first degree relative affected, suggesting another monogenic disease. PRKN 2 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 PRKN 2 mutations than patients with unilateral akinetic rigid parkinsonism and age at onset later than 40 years. As expected in a recessive disease, PRKN 2 patients present more often with affected siblings and unaffected patients. The G2019S LRRK 2 mutation, less prevalent than R1441G in our area, may be also a frequent cause of PD in EOPD (4 patients).