Haplotype analysis of Lrrk2 R1441H carriers with parkinsonism - PubMed (original) (raw)

doi: 10.1016/j.parkreldis.2008.09.001. Epub 2008 Oct 26.

Cleanthe Spanaki, Alida Griffith, Chin-Hsien Lin, Jennifer Kachergus, Kristoffer Haugarvoll, Helen Latsoudis, Andreas Plaitakis, Joaquim J Ferreira, Cristina Sampaio, Vincenzo Bonifati, Ruey-Meei Wu, Cyrus P Zabetian, Matthew J Farrer

Affiliations

Haplotype analysis of Lrrk2 R1441H carriers with parkinsonism

Owen A Ross et al. Parkinsonism Relat Disord. 2009 Jul.

Abstract

The Roc domain of the Lrrk2 protein harbors two pathogenic mutations which cause autosomal dominant parkinsonism (R1441C and R1441G). A third putatively pathogenic variant (R1441H) has been identified in four probands of diverse ethnicity with parkinsonism. Herein we show that the R1441H substitutions lie on different haplotypes within our patients, confirming this codon as a mutational hotspot. The absence of this variant in control subjects and the presence of two other pathogenic variants at this amino acid position collectively support the contention that R1441H is a pathogenic substitution.

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References

    1. Di Fonzo A, Wu-Chou YH, Lu CS, van Doeselaar M, Simons EJ, Rohe CF, et al. A common missense variant in the LRRK2 gene, Gly2385Arg, associated with Parkinson’s disease risk in Taiwan. Neurogenetics. 2006;7(3):133–8. - PubMed
    1. Mata IF, Wedemeyer WJ, Farrer MJ, Taylor JP, Gallo KA. LRRK2 in Parkinson’s disease: protein domains and functional insights. Trends Neurosci. 2006;29(5):286–93. - PubMed
    1. Ross OA, Wu YR, Lee MC, Funayama M, Chen ML, Soto AI, et al. Analysis of Lrrk2 R1628P as a risk factor for Parkinson’s disease. Ann Neurol. 2008;64:88–92. - PubMed
    1. Mata IF, Kachergus JM, Taylor JP, Lincoln S, Aasly J, Lynch T, et al. Lrrk2 pathogenic substitutions in Parkinson’s disease. Neurogenetics. 2005;6(4):171–7. - PubMed
    1. Zabetian CP, Samii A, Mosley AD, Roberts JW, Leis BC, Yearout D, et al. A clinic-based study of the LRRK2 gene in Parkinson disease yields new mutations. Neurology. 2005;65(5):741–4. - PubMed

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