A common LRRK2 mutation in idiopathic Parkinson's disease

Lancet. 2005;365(9457):415-6. doi: 10.1016/S0140-6736(05)17830-1.

Abstract

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have been shown to cause autosomal dominant Parkinson's disease. Few mutations in this gene have been identified. We investigated the frequency of a common heterozygous mutation, 2877510 g-->A, which produces a glycine to serine aminoacid substitution at codon 2019 (Gly2019 ser), in idiopathic Parkinson's disease. We assessed 482 patients with the disorder, of whom 263 had pathologically confirmed disease, by direct sequencing for mutations in exon 41 of LRRK2. The mutation was present in eight (1.6%) patients. We have shown that a common single Mendelian mutation is implicated in sporadic Parkinson's disease. We suggest that testing for this mutation will be important in the management and genetic counselling of patients with Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amino Acid Substitution
  • Brain / pathology
  • Heterozygote
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Middle Aged
  • Parkinson Disease / genetics*
  • Parkinson Disease / pathology
  • Point Mutation*
  • Protein Serine-Threonine Kinases / genetics*

Substances

  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Protein Serine-Threonine Kinases