TY - JOUR
T1 - Genetic analysis of LRRK2 mutations in patients with Parkinson disease
AU - Deng, Hao
AU - Le, Wei Dong
AU - Guo, Yi
AU - Hunter, Christine B.
AU - Xie, Wen Jie
AU - Huang, Mao Sheng
AU - Jankovic, Joseph
N1 - Funding Information:
Supported by grants NS 043567 and NS 40370 from the National Institute of Neurological Disorders and Stroke and from the National Parkinson Foundation to the Baylor College of Medicine Center of Excellence. The authors thank the participating patients for their cooperation, and thank Dr. William Ondo, and MS Kevin Dat Vuong (Parkinson disease Center and Movement Disorder Clinic, Baylor College of Medicine, Houston, TX) for their efforts in collecting the genetic information and DNA specimens.
PY - 2006/12/21
Y1 - 2006/12/21
N2 - In addition to the G2019S mutation in the leucine-rich repeat kinase 2 gene (LRRK2), which is particularly frequent in patients of Ashkenazi Jewish and Northern African origin, three amino acid substitutions (R1441C, R1441G, and R1441H), all at the same residue (R1441), have been identified as important genetic causes of Parkinson disease (PD). To evaluate the frequency of R1441C/G/H and G2019S mutations in the LRRK2 gene in North American patients with PD and to explore genotype-phenotype correlations, we screened 496 PD patients from North America. One Hispanic female was heterozygous for the LRRK2 R1441G mutation, and six other cases including 2 non-Jewish/non-Hispanic whites, 3 Ashkenazi Jewish, and 1 Hispanic, were found to be heterozygous for the LRRK2 G2019S mutation. G2019S mutation in the LRRK2 gene is a common mutation associated with PD in a North American population, especially in Jewish PD patients (10.7%), while the R1441C/G/H mutation occurs at a relatively low frequency in North Americans except possibly in Hispanics for R1441G. All six G2019S carriers shared a common haplotype with that observed in Europeans and North Africans. The clinical features of all seven cases with LRRK2 mutation were quite broad and included early and late disease onset. These finding may provide new insights into the cause and diagnosis of PD and have implications for genetic counseling.
AB - In addition to the G2019S mutation in the leucine-rich repeat kinase 2 gene (LRRK2), which is particularly frequent in patients of Ashkenazi Jewish and Northern African origin, three amino acid substitutions (R1441C, R1441G, and R1441H), all at the same residue (R1441), have been identified as important genetic causes of Parkinson disease (PD). To evaluate the frequency of R1441C/G/H and G2019S mutations in the LRRK2 gene in North American patients with PD and to explore genotype-phenotype correlations, we screened 496 PD patients from North America. One Hispanic female was heterozygous for the LRRK2 R1441G mutation, and six other cases including 2 non-Jewish/non-Hispanic whites, 3 Ashkenazi Jewish, and 1 Hispanic, were found to be heterozygous for the LRRK2 G2019S mutation. G2019S mutation in the LRRK2 gene is a common mutation associated with PD in a North American population, especially in Jewish PD patients (10.7%), while the R1441C/G/H mutation occurs at a relatively low frequency in North Americans except possibly in Hispanics for R1441G. All six G2019S carriers shared a common haplotype with that observed in Europeans and North Africans. The clinical features of all seven cases with LRRK2 mutation were quite broad and included early and late disease onset. These finding may provide new insights into the cause and diagnosis of PD and have implications for genetic counseling.
KW - Ashkenazi Jewish
KW - G2019S
KW - Mutation
KW - Parkinson disease
KW - R1441C/G/H
KW - The leucine-rich repeat kinase 2 gene
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U2 - 10.1016/j.jns.2006.09.017
DO - 10.1016/j.jns.2006.09.017
M3 - Article
C2 - 17097110
AN - SCOPUS:33751227461
SN - 0022-510X
VL - 251
SP - 102
EP - 106
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
IS - 1-2
ER -