1. R1514Q substitution in Lrrk2 is not a pathogenic Parkinson's disease mutation
- Author
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Karen Williams, Carolyn Peterson, S. Narayan, Margaret F. Turk, Julie H. Carter, C. Schell, Carlos Singer, Chad W. Christine, Paul J. Tuite, Robyn Schacherer, J. Whetteckey, S. Phipps, Diane K. Marek, William C. Nichols, John M. Bertoni, A. H. Rajput, Kenneth Marek, An Tran, P. Ryan, J. Hevezi, Joan Werner, Kelvin L. Chou, S. Chouinard, James Sutton, Margaret C. Lannon, T. Ajax, Joan Young, Deborah Judd, L. Zelaya, David Grimes, Magali Fernandez, Theresa A. Zesiewicz, Mark Stacy, Peggy Gray, Debra Berry, Michael J. Aminoff, C. Horn, C. Costan-Toth, J. Mannetter, Patricia Simpson, Susan Rolandelli, Tatiana Foroud, T. Tra, S. Wilson, Judith Dobson, Nestor Galvez-Jimenez, Donna Schwieterman, Shirley Uy, K. Price, J. Wojcieszek, Anette Nieves, Paul Atchison, Susan Bennett, L. Klassen, A. Podichetty, Vincent Calabrese, Becky Dunlop, D. Kamp, Holly Delgado, Sandra Roque, Maureen A. Leehey, Richard Camicioli, Julie So, Jayaraman Rao, Kelly E. Lyons, Kapil D. Sethi, A. Wang, Lynn Marlor, David Oakes, S. Culver, Juan Sanchez-Ramos, L. Woodward, J. Danielson, Jeannine Petit, Joann Belden, E. Licari, M. Meacham, Deborah Fontaine, Sharon Evans, C. Stone, S. Morehouse, Christopher F. O'Brien, G. Podskalny, J. Fraser, Anthony E. Lang, W.R. Wayne Martin, Carmen Serrano, H. Poiffaut, Stewart A. Factor, Joanne Wojcieszek, S. Belber, L. Davis, C. Allen, J. Hall, Judy Richman, Joseph Jankovic, Carson Reider, Stephen G. Reich, Stephanie Thomas, Kathy Davis, Richard B. Dewey, Karen Marder, T. Demarcaida, A. Kaczmarek, Lauren Seeberger, C. Halter, Mary Lou Klimek, Donald S. Higgins, Miodrag Velickovic, Joanna Hamann, Eric Siemers, E. Ohmann, C. Dingmann, Galit Kleiner-Fisman, Shari Niswonger, Theresa Derian, Maryan DeAngelis, Aileen Shinaman, Tilak Mendis, M. Rundle, Susan Mendick, L. Giffin, Karen Blindauer, Paul Gordon, Andrew Feigin, L. Shulman, Maureen Cook, Brian Wulbrecht, Rajesh Pahwa, T. Foroud, Un Jung Kang, Arthur Watts, Oksana Suchowersky, C. Joubert, J. Vo, Mandar Jog, M. Panisset, Roberta Winnick, Ronald F. Pfeiffer, Barbara Shannon, Jean P. Hubble, Clifford W. Shults, T. Gales, Tanya Simuni, M. Wolff, Hubert H. Fernandez, Pam Andrews, Karyn Boyar, Brad A. Racette, Vicki Hunt, Christine Hunter, Daniel D. Truong, L. Good, Robert L. Rodnitzky, P. Rodriguez, Sandra K. Kostyk, T. Shirley, Cheryl Halter, Peter A LeWitt, W. Weiner, Ryan J. Uitti, Lisa Scollins, Marc L. Gordon, J. Carpenter, Alice Rudolph, Lewis Sudarsky, Robert A. Hauser, Cliff Shults, Bala V. Manyam, Francis O. Walker, Juliette Harris, Marguerite Wieler, K. Dustin, Kelli Williamson, Brenda Pfeiffer, William C. Koller, Frederick J. Marshall, V. Hagen, A. Campbell, B. Hutchinson, L. Elmer, Anja Rudolph, K. Haas, Tori Ross, Rachel Saunders-Pullman, Nathan Pankratz, E. Aiken, Mariann DiMinno, Peggy Roberge, Arif Dalvi, B. Hayward, Mayank Pathak, David Simon, Michael W. Pauciulo, Holly A. Shill, M. Marotta-Kollarus, K. Ligon, Alok Sahay, Joseph H. Friedman, Neal Hermanowicz, E. Julian-Baros, Irenita Gardiner, N. Luong, Danna Jennings, R. Kurlan, and P. M. Conneally
- Subjects
Adult ,Male ,Parkinson's disease ,Adolescent ,Genotype ,Arginine ,Guanine ,Protein Serine-Threonine Kinases ,Biology ,Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 ,medicine.disease_cause ,Diagnosis, Differential ,chemistry.chemical_compound ,Degenerative disease ,medicine ,Humans ,Point Mutation ,Aged ,Aged, 80 and over ,Genetics ,Mutation ,Substitution (logic) ,Adenine Nucleotide Translocator 1 ,Genetic Variation ,Parkinson Disease ,Middle Aged ,medicine.disease ,LRRK2 ,nervous system diseases ,Amino Acid Substitution ,Neurology ,chemistry ,Female ,Neurology (clinical) ,Carrier Proteins - Abstract
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.
- Published
- 2007