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LRRK2 in Parkinson's disease: genetic and clinical studies from patients.
FEBS J. 2009 Nov; 276(22):6455-63.FJ

Abstract

Mutations in leucine-rich repeat kinase 2 (LRRK2) (PARK8) are associated with both familial and sporadic forms of Parkinson's disease. Most studies have shown that LRRK2 mutations may explain between 5% and 13% of familial and 1-5% of sporadic Parkinson's disease. Importantly, a common recurrent mutation (G2019S) located in the kinase domain has been reported across most ethnic populations, with the highest prevalence among Ashkenazi Jews and North African Arabs. A recent worldwide meta-analysis pooling data from 24 populations reported a higher occurrence of G2019S in southern than in northern European countries and the penetrance is estimated to be approximately 75% at the age of 79 years. The R1441 'hotspot' amino acid codon residue (G/H/C) in the Ras of complex proteins domain is the second most common site of pathogenic LRRK2 substitutions after G2019S, with most carriers developing symptoms by the age of 75 years. Two polymorphic variants found almost exclusively among Asians (G2385R and R1628P) have been shown to increase the Parkinson's disease risk by approximately two-fold. The mutational event associated with R1628P is more recent, occurring approximately 2500 years ago, compared to estimates of 4000 years for G2385R carriers. LRRK2 mutation carriers generally simulate late onset Parkinson's disease and present with the usual typical clinical features. Genetic testing for G2019S in sporadic late-onset Parkinson's disease can be considered in some situations and may be useful in populations with high carrier status. The identification of asymptomatic mutation and risk variant carriers provides a unique opportunity for recruiting these subjects in potential neuroprotective trials and longitudinal studies to identify biomarkers of neurodegeneration.

Authors+Show Affiliations

Department of Neurology, Singapore General Hospital, Singapore, Singapore.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

19804413

Citation

Kumari, Udhaya, and E K. Tan. "LRRK2 in Parkinson's Disease: Genetic and Clinical Studies From Patients." The FEBS Journal, vol. 276, no. 22, 2009, pp. 6455-63.
Kumari U, Tan EK. LRRK2 in Parkinson's disease: genetic and clinical studies from patients. FEBS J. 2009;276(22):6455-63.
Kumari, U., & Tan, E. K. (2009). LRRK2 in Parkinson's disease: genetic and clinical studies from patients. The FEBS Journal, 276(22), 6455-63. https://doi.org/10.1111/j.1742-4658.2009.07344.x
Kumari U, Tan EK. LRRK2 in Parkinson's Disease: Genetic and Clinical Studies From Patients. FEBS J. 2009;276(22):6455-63. PubMed PMID: 19804413.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - LRRK2 in Parkinson's disease: genetic and clinical studies from patients. AU - Kumari,Udhaya, AU - Tan,E K, Y1 - 2009/10/05/ PY - 2009/10/7/entrez PY - 2009/10/7/pubmed PY - 2010/2/19/medline SP - 6455 EP - 63 JF - The FEBS journal JO - FEBS J VL - 276 IS - 22 N2 - Mutations in leucine-rich repeat kinase 2 (LRRK2) (PARK8) are associated with both familial and sporadic forms of Parkinson's disease. Most studies have shown that LRRK2 mutations may explain between 5% and 13% of familial and 1-5% of sporadic Parkinson's disease. Importantly, a common recurrent mutation (G2019S) located in the kinase domain has been reported across most ethnic populations, with the highest prevalence among Ashkenazi Jews and North African Arabs. A recent worldwide meta-analysis pooling data from 24 populations reported a higher occurrence of G2019S in southern than in northern European countries and the penetrance is estimated to be approximately 75% at the age of 79 years. The R1441 'hotspot' amino acid codon residue (G/H/C) in the Ras of complex proteins domain is the second most common site of pathogenic LRRK2 substitutions after G2019S, with most carriers developing symptoms by the age of 75 years. Two polymorphic variants found almost exclusively among Asians (G2385R and R1628P) have been shown to increase the Parkinson's disease risk by approximately two-fold. The mutational event associated with R1628P is more recent, occurring approximately 2500 years ago, compared to estimates of 4000 years for G2385R carriers. LRRK2 mutation carriers generally simulate late onset Parkinson's disease and present with the usual typical clinical features. Genetic testing for G2019S in sporadic late-onset Parkinson's disease can be considered in some situations and may be useful in populations with high carrier status. The identification of asymptomatic mutation and risk variant carriers provides a unique opportunity for recruiting these subjects in potential neuroprotective trials and longitudinal studies to identify biomarkers of neurodegeneration. SN - 1742-4658 UR - https://www.unboundmedicine.com/medline/citation/19804413/LRRK2_in_Parkinson's_disease:_genetic_and_clinical_studies_from_patients_ L2 - https://doi.org/10.1111/j.1742-4658.2009.07344.x DB - PRIME DP - Unbound Medicine ER -