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The leucine rich repeat kinase 2 (LRRK2) G2019S substitution mutation

Association with Parkinson disease, malignant melanoma and prevalence in ethnic groups in Israel

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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.

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Authors and Affiliations

  1. The Parkinson’s Disease and Movement Disorders Clinic, Dept. of Neurology and Sagol Neuroscience Center, Chaim Sheba Medical Center, Tel-Hashomer, 52621, Israel

    Sharon Hassin-Baer MD, Irena Molchadski MSc & Oren S. Cohen MD

  2. The Susanne-Levy Gertner Oncogenetics Unit, The Institute of Human Genetics, Chaim Sheba Medical Center, Tel-Hashomer, 52621, Israel

    Yael Laitman MSc, Gilli Galore-Haskel MSc & Eitan Friedman MD, PhD

  3. The Department of Dermatology, Chaim Sheba Medical Center, Tel-Hashomer, 52621, Israel

    Esther Azizi MD

  4. The Oncology Institute, Barzilai Medical Center, Ashkelon, Israel

    Frida Barak MD

Authors
  1. Sharon Hassin-Baer MD
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  2. Yael Laitman MSc
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  3. Esther Azizi MD
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  4. Irena Molchadski MSc
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  5. Gilli Galore-Haskel MSc
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  6. Frida Barak MD
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  7. Oren S. Cohen MD
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  8. Eitan Friedman MD, PhD
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Corresponding author

Correspondence to Sharon Hassin-Baer MD.

Additional information

S. Hassin-Baer, MD · E. Azizi, MD · O. S. Cohen, MD · E. Friedman, MD, PhD Are affiliated to the Sackler School of medicine Tel-Aviv University Ramat Aviv, Tel Aviv, Israel

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Hassin-Baer, S., Laitman, Y., Azizi, E. et al. The leucine rich repeat kinase 2 (LRRK2) G2019S substitution mutation. J Neurol 256, 483–487 (2009). https://doi.org/10.1007/s00415-009-0117-x

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  • DOI: https://doi.org/10.1007/s00415-009-0117-x

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