The leucine rich repeat kinase 2 (LRRK2) G2019S substitution mutation: AAssociation with Parkinson disease, malignant melanoma and prevalence in ethnic groups in Israel

Sharon Hassin-Baer, Yael Laitman, Esther Azizi, Irena Molchadski, Gilli Galore-Haskel, Frida Barak, Oren S. Cohen, Eitan Friedman

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Background : A single missense mutation (G2019S) in the leucine rich repeat kinase 2 (LRRK2) gene has been reported to be prevalent among Ashkenazi Jewish patients with Parkinson disease (PD). An association between malignant melanoma (MM) and PD was also recently reported. The nature of this association is still elusive. Objective : To evaluate the rate of the G2019S* LRKK2 mutation among ethnically diverse, Jewish PD patients, MM patients, and Ashkenazi, Iraqi and Moroccan healthy controls. Patients and methods : Overall, 242 Jewish PD patients (155 Ashkenazim and 7 of mixed origin) and 169 Jewish MM patients (142 Ashkenazim) were genotyped for the G2019S mutation. In addition, 900 healthy ethnic Jewish controls (300 Ashkenazim, 300 Moroccans and 300 Iraqis) were similarly analyzed. Genotyping was performed using PCR amplification followed by restriction digest and gel electrophoresis. Statistical analysis was done using the Chi square test. Results : Overall 19/242 (7.9 %) of the PD patients (16/155 of Ashkenazim, 10.3 %; 3/87 of non-Ashkenazim, 3.4 %) harbored the G2019S LRKK2 mutation. The age at diagnosis of PD in mutation carriers was 60.6 ± 10.9 years compared with an age at diagnosis of 61.1 ± 13.4 years in non-carriers (p = 0.87). Nine of 38 familial Ashkenazi PD patients (23.68 %) carried the mutation, as did 2/169 MM patients (1.2 %; 2/142, 1.4 % of the Ashkenazim). A single mutation carrier of Ashkenazi origin was detected among 900 controls (0.3 % of the Ashkenazi controls). Conclusion : The G2019S*LRKK2 mutation is significantly more prevalent in Ashkenazi PD patients than in controls (p = 1 × 10 -6), it is less commonly detected in non-Ashkenazi affected individuals, and its contribution to MM predisposition in Jewish individuals needs to be explored further.

Original languageEnglish
Pages (from-to)483-487
Number of pages5
JournalJournal of Neurology
Volume256
Issue number3
DOIs
StatePublished - 1 Mar 2009
Externally publishedYes

Keywords

  • Germline mutation
  • Inherited predisposition
  • LRKK2 gene
  • Malignant melanoma
  • Parkinson's disease

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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