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Mutations in the Parkinson's disease genes, Leucine Rich Repeat Kinase 2 (LRRK2) and Glucocerebrosidase (GBA), are not associated with essential tremor.
Parkinsonism Relat Disord. 2010 Feb; 16(2):132-5.PR

Abstract

We evaluated an association between essential tremor (ET) and the Parkinson's disease (PD) genes, Leucine Rich Repeat Kinase 2 (LRRK2) and Glucocerebrosidase (GBA). Clinical studies demonstrate an association between ET and PD, suggesting possible shared pathophysiologies, yet LRRK2 has rarely been studied in ET, and GBA, not at all. ET cases (n = 275, including 42 with rest tremor) and controls (n = 289) were enrolled in an epidemiological study (Columbia University). Post-mortem brain tissue samples were obtained on 24 additional ET cases, including 3 with brainstem Lewy bodies. We performed a comprehensive analysis of the LRRK2 gene by genotyping 4 LRRK2 mutations (G2019S, I2020T, R1441C and Y1699C), 2 rare LRRK2 variants (L1114L and I1122V) and 19 LRRK2 SNPs. All GBA exons were sequenced in a subset of 93 Ashkenazi Jewish (AJ) cases, 62 AJ controls and 24 ET brains. LRRK2 mutations were not found in any ET cases or ET brains and none of the LRRK2 SNPs was associated with ET. GBA mutations were found in 7.5% (7/93) of AJ ET cases and 4.8% (3/62) of AJ controls (p = 0.75). 8.3% (2/24) of ET brains carried a GBA mutation. Four different heterozygous mutations were identified, including 3 previously reported mutations (N370S, R496H, and E326K) and 1 new missense variant (R44C). As suggested by several smaller prior reports, the known mutations for the LRRK2 gene are not risk factors for ET. Furthermore, a similar frequency of GBA mutations in AJ ET cases and controls suggests that GBA is not a common cause of ET either.

Authors+Show Affiliations

Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, NY, NY 10032, USA. LC654@columbia.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19527940

Citation

Clark, Lorraine N., et al. "Mutations in the Parkinson's Disease Genes, Leucine Rich Repeat Kinase 2 (LRRK2) and Glucocerebrosidase (GBA), Are Not Associated With Essential Tremor." Parkinsonism & Related Disorders, vol. 16, no. 2, 2010, pp. 132-5.
Clark LN, Kisselev S, Park N, et al. Mutations in the Parkinson's disease genes, Leucine Rich Repeat Kinase 2 (LRRK2) and Glucocerebrosidase (GBA), are not associated with essential tremor. Parkinsonism Relat Disord. 2010;16(2):132-5.
Clark, L. N., Kisselev, S., Park, N., Ross, B., Verbitsky, M., Rios, E., Alcalay, R. N., Lee, J. H., & Louis, E. D. (2010). Mutations in the Parkinson's disease genes, Leucine Rich Repeat Kinase 2 (LRRK2) and Glucocerebrosidase (GBA), are not associated with essential tremor. Parkinsonism & Related Disorders, 16(2), 132-5. https://doi.org/10.1016/j.parkreldis.2009.05.008
Clark LN, et al. Mutations in the Parkinson's Disease Genes, Leucine Rich Repeat Kinase 2 (LRRK2) and Glucocerebrosidase (GBA), Are Not Associated With Essential Tremor. Parkinsonism Relat Disord. 2010;16(2):132-5. PubMed PMID: 19527940.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mutations in the Parkinson's disease genes, Leucine Rich Repeat Kinase 2 (LRRK2) and Glucocerebrosidase (GBA), are not associated with essential tremor. AU - Clark,Lorraine N, AU - Kisselev,Sergey, AU - Park,Naeun, AU - Ross,Barbara, AU - Verbitsky,Miguel, AU - Rios,Eileen, AU - Alcalay,Roy N, AU - Lee,Joseph H, AU - Louis,Elan D, Y1 - 2009/06/13/ PY - 2009/01/13/received PY - 2009/05/14/revised PY - 2009/05/17/accepted PY - 2009/6/17/entrez PY - 2009/6/17/pubmed PY - 2010/5/5/medline SP - 132 EP - 5 JF - Parkinsonism & related disorders JO - Parkinsonism Relat Disord VL - 16 IS - 2 N2 - We evaluated an association between essential tremor (ET) and the Parkinson's disease (PD) genes, Leucine Rich Repeat Kinase 2 (LRRK2) and Glucocerebrosidase (GBA). Clinical studies demonstrate an association between ET and PD, suggesting possible shared pathophysiologies, yet LRRK2 has rarely been studied in ET, and GBA, not at all. ET cases (n = 275, including 42 with rest tremor) and controls (n = 289) were enrolled in an epidemiological study (Columbia University). Post-mortem brain tissue samples were obtained on 24 additional ET cases, including 3 with brainstem Lewy bodies. We performed a comprehensive analysis of the LRRK2 gene by genotyping 4 LRRK2 mutations (G2019S, I2020T, R1441C and Y1699C), 2 rare LRRK2 variants (L1114L and I1122V) and 19 LRRK2 SNPs. All GBA exons were sequenced in a subset of 93 Ashkenazi Jewish (AJ) cases, 62 AJ controls and 24 ET brains. LRRK2 mutations were not found in any ET cases or ET brains and none of the LRRK2 SNPs was associated with ET. GBA mutations were found in 7.5% (7/93) of AJ ET cases and 4.8% (3/62) of AJ controls (p = 0.75). 8.3% (2/24) of ET brains carried a GBA mutation. Four different heterozygous mutations were identified, including 3 previously reported mutations (N370S, R496H, and E326K) and 1 new missense variant (R44C). As suggested by several smaller prior reports, the known mutations for the LRRK2 gene are not risk factors for ET. Furthermore, a similar frequency of GBA mutations in AJ ET cases and controls suggests that GBA is not a common cause of ET either. SN - 1873-5126 UR - https://www.unboundmedicine.com/medline/citation/19527940/Mutations_in_the_Parkinson's_disease_genes_Leucine_Rich_Repeat_Kinase_2__LRRK2__and_Glucocerebrosidase__GBA__are_not_associated_with_essential_tremor_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1353-8020(09)00134-5 DB - PRIME DP - Unbound Medicine ER -