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LRRK2 Gene (lrrk2 + gene)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Screening for SNCA and LRRK2 mutations in Greek sporadic and autosomal dominant Parkinson's disease: identification of two novel LRRK2 variants

EUROPEAN JOURNAL OF NEUROLOGY, Issue 1 2007
G. Xiromerisiou
Mutations in SNCA and LRRK2 genes, encoding alpha-synuclein and leucine-rich repeat kinase 2, respectively, cause autosomal dominant Parkinson's disease (AdPD). The LRRK2 G2019S (c.6055G > A) and R1441G (c.4321C > G) mutations have also been identified in sporadic PD (sPD). We studied 55 unrelated patients with AdPD, 235 patients with sPD, and 235 healthy age- and gender-matched controls all of Greek origin. Patients with AdPD were screened for SNCA and LRRK2 mutations by direct sequencing. SNCA gene dosage analysis was also performed for AdPD using quantitative duplex polymerase chain reaction of genomic DNA. In addition, we investigated the frequency of the LRRK2 G2019S mutation in sPD. We found no missense mutations or multiplications in the SNCA gene. Here we report two novel variants, A211V (c.632C > T) and K544E (c.1630A > G) in LRRK2 gene in two patients with AdPD that was not present in controls. We identified only one patient with sPD (1/235; 0.4%) carrying the G2019S mutation. LRRK2 mutations are present in AdPD and sPD patients of Greek origin. [source]

Parkinson's disease and LRRK2: Frequency of a common mutation in U.S. movement disorder clinics

MOVEMENT DISORDERS, Issue 4 2006
Denise M. Kay PhD
Abstract The G2019S mutation in the LRRK2 gene is reportedly a common cause of familial Parkinson's disease (PD) and may also have a significant role in nonfamilial PD. The objective of this study was to assess mutation carrier frequency in PD patients from movement disorder clinics in the United States, stratified by family history, age at onset, and geography; to determine carrier frequency in a large and well-characterized control population; to examine segregation of mutation in families of patients; and to correlate genotype with clinical phenotype. One thousand four hundred twenty-five unrelated PD patients from movement disorder clinics in Oregon, Washington, and New York and 1,647 unrelated controls were studied. The G2019S mutation was detected using a TaqMan assay and verified by sequencing. Eighteen of 1,425 patients and one of 1,647 controls had the mutation. Carrier frequency (± 2SE) in patients was 0.013 ± 0.006 overall, 0.030 ± 0.019 in familial PD, 0.007 ± 0.005 in nonfamilial PD, 0.016 ± 0.013 in early-onset PD, and 0.012 ± 0.007 in late-onset PD. Geographic differences were insignificant. Age at onset of mutation carriers ranged from 28 to 71 years. Mutation carriers were clinically indistinguishable from idiopathic PD. LRRK2 G2019S is the single most common pathogenic mutation linked to neurodegenerative disease to date. © 2005 Movement Disorder Society [source]

LRRK2 and Parkinson's disease in Norway

ACTA NEUROLOGICA SCANDINAVICA, Issue 2007
M. Toft
Objectives, Mutations in the LRRK2 gene have been associated with both familial and sporadic late-onset Parkinson's disease. A large number of mutations in this gene have been identified; however, for many of these variants, the pathogenicity and relative frequency are unknown. Herein, we investigate the frequency of a number of recently identified LRRK2 mutations in Norway. Methods, We genotyped eight putatively pathogenic LRRK2 mutations (R793M, R1067Q, I1371V, IVS31+3 A>G, M1869T, R1941H, T2356I and G2385R) in a series of 433 patients with Parkinson's disease and 587 controls from Norway. An intronic polymorphism previously reported to be associated with disease susceptibility was also examined (rs10506151). Results, The Lrrk2 R793M substitution was found in two healthy individuals. No other LRRK2 mutations were identified in the Norwegian population, and furthermore no association was observed between rs10506151 and Parkinson's disease (P = 0.41). Conclusions,LRRK2 mutations other than the Lrrk2 G2019S mutation are rare in Norway. Our results indicate that the Lrrk2 R793M substitution is most likely a rare polymorphism. [source]