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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adult
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Arginine / genetics
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DNA Mutational Analysis
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Female
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Gene Frequency
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Genetic Predisposition to Disease*
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Haplotypes
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Histidine / genetics
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Humans
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Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
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Male
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Middle Aged
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Parkinsonian Disorders / genetics*
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Polymorphism, Single Nucleotide / genetics*
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Protein Serine-Threonine Kinases / genetics*
Substances
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Histidine
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Arginine
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LRRK2 protein, human
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Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
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Protein Serine-Threonine Kinases