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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 254-256 |
| Number of pages | 3 |
| Journal | Movement Disorders |
| Volume | 22 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jan 15 2007 |
| Externally published | Yes |
All Science Journal Classification (ASJC) codes
- Neurology
- Clinical Neurology
Keywords
- Genetics
- LRRK2
- Mutation
- Parkinson's disease
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R1514Q substitution in Lrrk2 is not a pathogenic Parkinson's disease mutation. / 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.; Lyons, K.; Siemers, E.; Factor, S.; Higgins, D.; Evans, S.; Shill, H.; Stacy, M.; Danielson, J.; Marlor, L.; Williamson, K.; Jankovic, J.; Hunter, C.; Simon, D.; Ryan, P.; Scollins, L.; Saunders-Pullman, R.; Boyar, K.; Costan-Toth, C.; Ohmann, E.; Sudarsky, L.; Joubert, C.; Friedman, J.; Chou, K.; Fernandez, H.; Lannon, M.; Galvez-Jimenez, N.; Podichetty, A.; Lewitt, P.; DeAngelis, M.; O'Brien, C.; Seeberger, L.; Dingmann, C.; Judd, D.; Marder, K.; Fraser, J.; Harris, J.; Bertoni, J.; Peterson, C.; Chouinard, S.; Panisset, M.; Hall, J.; Poiffaut, H.; Calabrese, V.; Roberge, P.; Wojcieszek, J.; Belden, J.; Halter, C.; Jennings, D.; Marek, K.; Mendick, S.; Reich, S.; Dunlop, B.; Jog, M.; Horn, C.; Rao, J.; Cook, M.; Uitti, R.; Turk, M.; Ajax, T.; Mannetter, J.; Panisset, M.; Hall, J.; Sethi, K.; Carpenter, J.; Ligon, K.; Narayan, S.; Woodward, L.; Blindauer, K.; Petit, J.; Elmer, L.; Aiken, E.; Davis, K.; Schell, C.; Wilson, S.; Velickovic, M.; Koller, W.; Phipps, S.; Feigin, A.; Gordon, M.; Hamann, J.; Licari, E.; Marotta-Kollarus, M.; Shannon, B.; Winnick, R.; Simuni, T.; Kaczmarek, A.; Williams, K.; Wolff, M.; Fernandez, M.; Hubble, J.; Kostyk, S.; Campbell, A.; Reider, C.; Camicioli, R.; Carter, J.; Andrews, P.; Morehouse, S.; Stone, C.; Mendis, T.; Grimes, D.; Gray, P.; Haas, K.; Sutton, J.; Hutchinson, B.; Young, J.; Rajput, A.; Rajput, A.; Klassen, L.; Shirley, T.; Manyam, B.; Simpson, P.; Whetteckey, J.; Wulbrecht, B.; Truong, D.; Pathak, M.; Luong, N.; Tra, T.; Tran, A.; Vo, J.; Lang, A.; Kleiner-Fisman, G.; Nieves, A.; So, J.; Podskalny, G.; Giffin, L.; Atchison, P.; Allen, C.; Martin, W.; Wieler, M.; Suchowersky, O.; Klimek, M.; Hermanowicz, N.; Niswonger, S.; Shults, C.; Fontaine, D.; Aminoff, M.; Christine, C.; Diminno, M.; Hevezi, J.; Dalvi, A.; Kang, U.; Richman, J.; Uy, S.; Young, J.; Dalvi, A.; Sahay, A.; Schwieterman, D.; Leehey, M.; Culver, S.; Derian, T.; Demarcaida, T.; Belber, S.; Rodnitzky, R.; Dobson, J.; Pahwa, R.; Lyons, K.; Gales, T.; Thomas, S.; Shulman, L.; Weiner, W.; Dustin, K.; Singer, C.; Koller, W.; Lyons, K.; Weiner, W.; Zelaya, L.; Tuite, P.; Hagen, V.; Rolandelli, S.; Schacherer, R.; Gordon, P.; Werner, J.; Serrano, C.; Roque, S.; Kurlan, R.; Berry, D.; Gardiner, I.; Hauser, R.; Sanchez-Ramos, J.; Zesiewicz, T.; Delgado, H.; Price, K.; Rodriguez, P.; Pfeiffer, R.; Davis, L.; Pfeiffer, B.; Dewey, R.; Hayward, B.; Meacham, M.; Walker, F.; Hunt, V.; Racette, B.; Good, L.; Rundle, M.; Watts, A.; Wang, A.; Ross, T.; Bennett, S.; Kamp, D.; Julian-Baros, E.
In: Movement Disorders, Vol. 22, No. 2, 15.01.2007, p. 254-256.Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - R1514Q substitution in Lrrk2 is not a pathogenic Parkinson's disease mutation
AU - Nichols, William C.
AU - Marek, Diane K.
AU - Pauciulo, Michael W.
AU - Pankratz, Nathan
AU - Halter, Cheryl A.
AU - Rudolph, Alice
AU - Shults, Clifford W.
AU - Wojcieszek, Joanne
AU - Foroud, Tatiana
AU - Shults, C.
AU - Marshall, F.
AU - Oakes, D.
AU - Rudolph, A.
AU - Shinaman, A.
AU - Marder, K.
AU - Conneally, P. M.
AU - Foroud, T.
AU - Halter, C.
AU - Lyons, K.
AU - Siemers, E.
AU - Factor, S.
AU - Higgins, D.
AU - Evans, S.
AU - Shill, H.
AU - Stacy, M.
AU - Danielson, J.
AU - Marlor, L.
AU - Williamson, K.
AU - Jankovic, J.
AU - Hunter, C.
AU - Simon, D.
AU - Ryan, P.
AU - Scollins, L.
AU - Saunders-Pullman, R.
AU - Boyar, K.
AU - Costan-Toth, C.
AU - Ohmann, E.
AU - Sudarsky, L.
AU - Joubert, C.
AU - Friedman, J.
AU - Chou, K.
AU - Fernandez, H.
AU - Lannon, M.
AU - Galvez-Jimenez, N.
AU - Podichetty, A.
AU - Lewitt, P.
AU - DeAngelis, M.
AU - O'Brien, C.
AU - Seeberger, L.
AU - Dingmann, C.
AU - Judd, D.
AU - Marder, K.
AU - Fraser, J.
AU - Harris, J.
AU - Bertoni, J.
AU - Peterson, C.
AU - Chouinard, S.
AU - Panisset, M.
AU - Hall, J.
AU - Poiffaut, H.
AU - Calabrese, V.
AU - Roberge, P.
AU - Wojcieszek, J.
AU - Belden, J.
AU - Halter, C.
AU - Jennings, D.
AU - Marek, K.
AU - Mendick, S.
AU - Reich, S.
AU - Dunlop, B.
AU - Jog, M.
AU - Horn, C.
AU - Rao, J.
AU - Cook, M.
AU - Uitti, R.
AU - Turk, M.
AU - Ajax, T.
AU - Mannetter, J.
AU - Panisset, M.
AU - Hall, J.
AU - Sethi, K.
AU - Carpenter, J.
AU - Ligon, K.
AU - Narayan, S.
AU - Woodward, L.
AU - Blindauer, K.
AU - Petit, J.
AU - Elmer, L.
AU - Aiken, E.
AU - Davis, K.
AU - Schell, C.
AU - Wilson, S.
AU - Velickovic, M.
AU - Koller, W.
AU - Phipps, S.
AU - Feigin, A.
AU - Gordon, M.
AU - Hamann, J.
AU - Licari, E.
AU - Marotta-Kollarus, M.
AU - Shannon, B.
AU - Winnick, R.
AU - Simuni, T.
AU - Kaczmarek, A.
AU - Williams, K.
AU - Wolff, M.
AU - Fernandez, M.
AU - Hubble, J.
AU - Kostyk, S.
AU - Campbell, A.
AU - Reider, C.
AU - Camicioli, R.
AU - Carter, J.
AU - Andrews, P.
AU - Morehouse, S.
AU - Stone, C.
AU - Mendis, T.
AU - Grimes, D.
AU - Gray, P.
AU - Haas, K.
AU - Sutton, J.
AU - Hutchinson, B.
AU - Young, J.
AU - Rajput, A.
AU - Rajput, A.
AU - Klassen, L.
AU - Shirley, T.
AU - Manyam, B.
AU - Simpson, P.
AU - Whetteckey, J.
AU - Wulbrecht, B.
AU - Truong, D.
AU - Pathak, M.
AU - Luong, N.
AU - Tra, T.
AU - Tran, A.
AU - Vo, J.
AU - Lang, A.
AU - Kleiner-Fisman, G.
AU - Nieves, A.
AU - So, J.
AU - Podskalny, G.
AU - Giffin, L.
AU - Atchison, P.
AU - Allen, C.
AU - Martin, W.
AU - Wieler, M.
AU - Suchowersky, O.
AU - Klimek, M.
AU - Hermanowicz, N.
AU - Niswonger, S.
AU - Shults, C.
AU - Fontaine, D.
AU - Aminoff, M.
AU - Christine, C.
AU - Diminno, M.
AU - Hevezi, J.
AU - Dalvi, A.
AU - Kang, U.
AU - Richman, J.
AU - Uy, S.
AU - Young, J.
AU - Dalvi, A.
AU - Sahay, A.
AU - Schwieterman, D.
AU - Leehey, M.
AU - Culver, S.
AU - Derian, T.
AU - Demarcaida, T.
AU - Belber, S.
AU - Rodnitzky, R.
AU - Dobson, J.
AU - Pahwa, R.
AU - Lyons, K.
AU - Gales, T.
AU - Thomas, S.
AU - Shulman, L.
AU - Weiner, W.
AU - Dustin, K.
AU - Singer, C.
AU - Koller, W.
AU - Lyons, K.
AU - Weiner, W.
AU - Zelaya, L.
AU - Tuite, P.
AU - Hagen, V.
AU - Rolandelli, S.
AU - Schacherer, R.
AU - Gordon, P.
AU - Werner, J.
AU - Serrano, C.
AU - Roque, S.
AU - Kurlan, R.
AU - Berry, D.
AU - Gardiner, I.
AU - Hauser, R.
AU - Sanchez-Ramos, J.
AU - Zesiewicz, T.
AU - Delgado, H.
AU - Price, K.
AU - Rodriguez, P.
AU - Pfeiffer, R.
AU - Davis, L.
AU - Pfeiffer, B.
AU - Dewey, R.
AU - Hayward, B.
AU - Meacham, M.
AU - Walker, F.
AU - Hunt, V.
AU - Racette, B.
AU - Good, L.
AU - Rundle, M.
AU - Watts, A.
AU - Wang, A.
AU - Ross, T.
AU - Bennett, S.
AU - Kamp, D.
AU - Julian-Baros, E.
N1 - Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2007/1/15
Y1 - 2007/1/15
N2 - 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.
AB - 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.
KW - Genetics
KW - LRRK2
KW - Mutation
KW - Parkinson's disease
UR - http://www.scopus.com/inward/record.url?scp=33847700524&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33847700524&partnerID=8YFLogxK
U2 - 10.1002/mds.21233
DO - 10.1002/mds.21233
M3 - Article
C2 - 17149721
AN - SCOPUS:33847700524
VL - 22
SP - 254
EP - 256
JO - Movement Disorders
JF - Movement Disorders
SN - 0885-3185
IS - 2
ER -