LOW DISEASE RISK IN RELATIVES OF NORTH AFRICAN LRRK2 PARKINSON DISEASE PATIENTS

Currently, mutations in the leucine repeat–rich kinase 2 (LRRK2) gene are the main identifiable genetic cause of Parkinson disease (PD). The Gly2019Ser (G2019S) substitution is the most common mutation and is frequent among North African (40%) and Jewish (30%) patients with familial PD. Reduced G2019S penetrance has been documented in several reports.1–3 The identification of LRRK2 mutations in numerous North African patients without PD family history prompted us to investigate disease risk in presumed mutation carriers in this population. ### Methods. PD cases were recruited by a national French network (French PD Genetic Study Group) and collaborators from Algeria at their outpatient clinic (September 1994 through August 2007). Blood samples were collected from participants after obtaining written informed consent, and molecular analyses were performed.4 For this study, we included probands of North African ancestry who were heterozygous or homozygous G2019S carriers (figure e-1 on the Neurology ® Web site at www.neurology.org). They were interviewed to obtain information on their first-degree relatives. Relatives were analyzed from birth through 1 of the following events, whichever occurred first: PD onset or last contact or death without PD. The cumulative risk of PD until age 80 years in first-degree relatives was estimated using the Kaplan-Meier …