R1514Q Substitution in LRRK2 is Not a Pathogenic Parkinson's Disease Mutation
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.
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Nichols, William C.; Marek, Diane K.; Pauciulo, Michael W.; Pankratz, Nathan; Halter, Cheryl A.; Rudolph, Alice; Shults, Clifford W.; Wojcieszek, Joanne; Foroud, Tatiana; Shults, C.; Marshall, F.; Oakes, D.; Rudolph, A.; Shinaman, A.; Marder, K.; Conneally, P. M.; Foroud, T.; Halter, C.; Shill, Holly A.; and al., et, "R1514Q Substitution in LRRK2 is Not a Pathogenic Parkinson's Disease Mutation" (2007). Neurology. 232.