Genetic analysis of LRRK2 mutations in patients with Parkinson disease

Hao Deng, WeiDong Le, Yi Guo, Christine B. Hunter, WenJie Xie, MaoSheng Huang, Joseph Jankovic

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)102-106
Number of pages5
JournalJournal of the Neurological Sciences
Volume251
Issue number1-2
DOIs
StatePublished - Dec 21 2006

Keywords

  • Ashkenazi Jewish
  • G2019S
  • Mutation
  • Parkinson disease
  • R1441C/G/H
  • The leucine-rich repeat kinase 2 gene

ASJC Scopus subject areas

  • Aging
  • Clinical Neurology
  • Surgery
  • Developmental Neuroscience
  • Neurology
  • Neuroscience(all)

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