R1514Q substitution in Lrrk2 is not a pathogenic Parkinson's disease mutation

Academic Article


  • Mutations in LRRK2 were first reported as causing Parkinson's disease (PD) in late 2004. Since then, approximately a dozen LRRK2 substitutions have been identified that are believed to be pathogenic mutations. The substitution of adenine for guanine at nucleotide 4541 (4541G>A) in LRRK2 was recently reported. This substitution resulted in the replacement of an arginine at position 1514 with a glutamine (R1514Q). Although this substitution was not found in a large cohort of controls, its pathogenicity could not be verified. We have now genotyped the R1514Q substitution in a sample of 954 PD patients from 429 multiplex PD families. This substitution was identified in 1.8% of the PD patients; however, the majority of the PD sibships segregating this substitution were discordant for this putative mutation. In addition, the R1514Q substitution was detected in 1.4% of neurologically evaluated, control individuals. These data suggest that the R1514Q variant is not a pathogenic LRRK2 mutation. We believe it is imperative that the causative nature of any newly identified genetic variant be determined before it is included in any panel for diagnostic testing. © 2006 Movement Disorder Society.
  • Authors

    Published In

  • Movement Disorders  Journal
  • Digital Object Identifier (doi)

    Author List

  • Nichols WC; Marek DK; Pauciulo MW; Pankratz N; Halter CA; Rudolph A; Shults CW; Wojcieszek J; Foroud T; Shults C
  • Start Page

  • 254
  • End Page

  • 256
  • Volume

  • 22
  • Issue

  • 2