LRRK2 PD: Founder Effect, Clinical and Radiologic Features

Subject: LRRK2 PD: Founder Effect, Clinical and Radiologic Features

Date: 3/11/2005

1. Identification of a novel LRRK2 mutation linked to autosomal dominant parkinsonism: Evidence of a common founder across European populations
J Kachergus, IF Mata, M Hulihan, JP Taylor, S Lincoln, J Aasly, JM Gibson, OA Ross, T Lynch, J Wiley, H Payami, J Nutt, DM Maraganore, K Czyzewski, M Styczynska, ZK Wszolek, MJ Farrer, M Toft
Am J Hum Genet 2005;76; epub ahead of print edition

The G2019S mutation of LRRK2 is a common cause of autosomal dominant PD in families of European origin, and accounts for a small proportion of sporadic cases, according to this study. LRRK2 is the gene at the PARK8 locus.

Of 248 affected probands from families with autosomal dominant PD, 7 (2.8%) had the G2019S mutation in LRRK2. An additional 6 patients with the mutation were identified through population-based screening, including 3 with no family history of PD. No mutation was identified in 2,260 controls. Patients were from Norway, the United States, Ireland, and Poland, and all shared a common ancestor. Age at onset of disease was variable, even within the same family, ranging from 39 to 78 years. Penetrance was age dependent, rising to 85% by age 70. Mean age at onset was 56.8 years. Unaffected carriers had a mean age of 54.6 years.

2. Clinical and positron emission tomography of Parkinson's disease caused by LRRK2
DG Hernandez, C Paisan-Ruiz, A McInerney-Leo, S Jain, A Meyer-Lindbergh, EW Evans, KF Berman, J Johnson, G Auberger, AA Schaffer, GJ Lopez, RL Nussbaum, AB Singleton
Ann Neurol 2005;57:453-456

Clinical and imaging characteristics of LRRK2 PD are similar to typical idiopathic PD, according to this study.

In 6 patients with confirmed LRRK2 mutations, age at onset ranged from 45-73. Presentation was with unilateral tremor, which progressed to bilateral. Disease progressed to involve rigidity and bradykinesia, as well as anosmia and difficulties of gait and balance. All patients who received levodopa showed benefit, and two developed dyskinesias after 7 years of treatment. One patient received unilateral pallidotomy and showed improvement. Neuroimaging in 2 patients showed abnormalities typical of PD, which were not seen in a genetically unaffected sibling or 3 next-generation family members.