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


Journal 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.

Full Text

Cited Authors

  • Nichols, WC; Marek, DK; Pauciulo, MW; Pankratz, N; Halter, CA; Rudolph, A; Shults, CW; Wojcieszek, J; Foroud, T; Parkinson Study Group - PROGENI Investigators,

Published Date

  • January 1, 2007

Published In

Volume / Issue

  • 22 / 2

Start / End Page

  • 254 - 257

PubMed ID

  • 17149721

Pubmed Central ID

  • 17149721

Electronic International Standard Serial Number (EISSN)

  • 1531-8257

International Standard Serial Number (ISSN)

  • 0885-3185

Digital Object Identifier (DOI)

  • 10.1002/mds.21233


  • eng