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

William C. Nichols; Diane K. Marek; Michael W. Pauciulo; Nathan Pankratz; Cheryl A. Halter; Alice Rudolph; Clifford W. Shults; Joanne Wojcieszek; Tatiana Foroud; C. Shults; F. Marshall; D. Oakes; A. Rudolph; A. Shinaman; K. Marder; P. M. Conneally; C. Halter; K. Lyons; E. Siemers; S. Factor; D. Higgins; S. Evans; H. Shill; M. Stacy; J. Danielson; L. Marlor; K. Williamson; J. Jankovic; C. Hunter; D. Simon; P. Ryan; L. Scollins; R. Saunders-Pullman; K. Boyar; C. Costan-Toth; E. Ohmann; L. Sudarsky; C. Joubert; J. Friedman; K. Chou; H. Fernandez; M. Lannon; N. Galvez-Jimenez; A. Podichetty; P. Lewitt; M. DeAngelis; C. O'Brien; L. Seeberger; C. Dingmann; D. Judd; K. Marder; J. Fraser; J. Harris; J. Bertoni; C. Peterson; S. Chouinard; M. Panisset; J. Hall; H. Poiffaut; V. Calabrese; P. Roberge; J. Wojcieszek; J. Belden; C. Halter; D. Jennings; K. Marek; S. Mendick; S. Reich; B. Dunlop; M. Jog; C. Horn; J. Rao; M. Cook; R. Uitti; M. Turk; T. Ajax; J. Mannetter; M. Panisset; J. Hall; K. Sethi; J. Carpenter; K. Ligon; S. Narayan; L. Woodward; K. Blindauer; J. Petit; L. Elmer; E. Aiken; K. Davis; C. Schell; S. Wilson; M. Velickovic; W. Koller; S. Phipps; A. Feigin; M. Gordon; J. Hamann; E. Licari; M. Marotta-Kollarus; B. Shannon; R. Winnick; T. Simuni; A. Kaczmarek; K. Williams; M. Wolff; M. Fernandez; J. Hubble; S. Kostyk; A. Campbell; C. Reider; R. Camicioli; J. Carter; P. Andrews; S. Morehouse; C. Stone; T. Mendis; D. Grimes; P. Gray; K. Haas; J. Sutton; B. Hutchinson; J. Young; A. Rajput; A. Rajput; L. Klassen; T. Shirley; B. Manyam; P. Simpson; J. Whetteckey; B. Wulbrecht; D. Truong; M. Pathak; N. Luong; T. Tra; A. Tran; J. Vo; A. Lang; G. Kleiner-Fisman; A. Nieves; J. So; G. Podskalny; L. Giffin; P. Atchison; C. Allen; W. Martin; M. Wieler; O. Suchowersky; M. Klimek; N. Hermanowicz; S. Niswonger; C. Shults; D. Fontaine; M. Aminoff; C. Christine; M. Diminno; J. Hevezi; A. Dalvi; U. Kang; J. Richman; S. Uy; J. Young; A. Dalvi; A. Sahay; D. Schwieterman; M. Leehey; S. Culver; T. Derian; T. Demarcaida; S. Belber; R. Rodnitzky; J. Dobson; R. Pahwa; K. Lyons; T. Gales; S. Thomas; L. Shulman; W. Weiner; K. Dustin; C. Singer; W. Koller; K. Lyons; W. Weiner; L. Zelaya; P. Tuite; V. Hagen; S. Rolandelli; R. Schacherer; P. Gordon; J. Werner; C. Serrano; S. Roque; R. Kurlan; D. Berry; I. Gardiner; R. Hauser; J. Sanchez-Ramos; T. Zesiewicz; H. Delgado; K. Price; P. Rodriguez; R. Pfeiffer; L. Davis; B. Pfeiffer; R. Dewey; B. Hayward; M. Meacham; F. Walker; V. Hunt; B. Racette; L. Good; M. Rundle; A. Watts; A. Wang; T. Ross; S. Bennett; D. Kamp; E. Julian-Baros

doi:10.1002/mds.21233

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

William C. Nichols, Diane K. Marek, Michael W. Pauciulo, Nathan Pankratz, Cheryl A. Halter, Alice Rudolph, Clifford W. Shults, Joanne Wojcieszek, Tatiana Foroud, C. Shults, F. Marshall, D. Oakes, A. Rudolph, A. Shinaman, K. Marder, P. M. Conneally, C. Halter, K. Lyons, E. Siemers, S. FactorD. Higgins, S. Evans, H. Shill, M. Stacy, J. Danielson, L. Marlor, K. Williamson, J. Jankovic, C. Hunter, D. Simon, P. Ryan, L. Scollins, R. Saunders-Pullman, K. Boyar, C. Costan-Toth, E. Ohmann, L. Sudarsky, C. Joubert, J. Friedman, K. Chou, H. Fernandez, M. Lannon, N. Galvez-Jimenez, A. Podichetty, P. Lewitt, M. DeAngelis, C. O'Brien, L. Seeberger, C. Dingmann, D. Judd, K. Marder, J. Fraser, J. Harris, J. Bertoni, C. Peterson, S. Chouinard, M. Panisset, J. Hall, H. Poiffaut, V. Calabrese, P. Roberge, J. Wojcieszek, J. Belden, C. Halter, D. Jennings, K. Marek, S. Mendick, S. Reich, B. Dunlop, M. Jog, C. Horn, J. Rao, M. Cook, R. Uitti, M. Turk, T. Ajax, J. Mannetter, M. Panisset, J. Hall, K. Sethi, J. Carpenter, K. Ligon, S. Narayan, L. Woodward, K. Blindauer, J. Petit, L. Elmer, E. Aiken, K. Davis, C. Schell, S. Wilson, M. Velickovic, W. Koller, S. Phipps, A. Feigin, M. Gordon, J. Hamann, E. Licari, M. Marotta-Kollarus, B. Shannon, R. Winnick, T. Simuni, A. Kaczmarek, K. Williams, M. Wolff, M. Fernandez, J. Hubble, S. Kostyk, A. Campbell, C. Reider, R. Camicioli, J. Carter, P. Andrews, S. Morehouse, C. Stone, T. Mendis, D. Grimes, P. Gray, K. Haas, J. Sutton, B. Hutchinson, J. Young, A. Rajput, A. Rajput, L. Klassen, T. Shirley, B. Manyam, P. Simpson, J. Whetteckey, B. Wulbrecht, D. Truong, M. Pathak, N. Luong, T. Tra, A. Tran, J. Vo, A. Lang, G. Kleiner-Fisman, A. Nieves, J. So, G. Podskalny, L. Giffin, P. Atchison, C. Allen, W. Martin, M. Wieler, O. Suchowersky, M. Klimek, N. Hermanowicz, S. Niswonger, C. Shults, D. Fontaine, M. Aminoff, C. Christine, M. Diminno, J. Hevezi, A. Dalvi, U. Kang, J. Richman, S. Uy, J. Young, A. Dalvi, A. Sahay, D. Schwieterman, M. Leehey, S. Culver, T. Derian, T. Demarcaida, S. Belber, R. Rodnitzky, J. Dobson, R. Pahwa, K. Lyons, T. Gales, S. Thomas, L. Shulman, W. Weiner, K. Dustin, C. Singer, W. Koller, K. Lyons, W. Weiner, L. Zelaya, P. Tuite, V. Hagen, S. Rolandelli, R. Schacherer, P. Gordon, J. Werner, C. Serrano, S. Roque, R. Kurlan, D. Berry, I. Gardiner, R. Hauser, J. Sanchez-Ramos, T. Zesiewicz, H. Delgado, K. Price, P. Rodriguez, R. Pfeiffer, L. Davis, B. Pfeiffer, R. Dewey, B. Hayward, M. Meacham, F. Walker, V. Hunt, B. Racette, L. Good, M. Rundle, A. Watts, A. Wang, T. Ross, S. Bennett, D. Kamp, E. Julian-Baros

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

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	https://doi.org/10.1002/mds.21233
State	Published - Jan 15 2007
Externally published	Yes

All Science Journal Classification (ASJC) codes

Neurology
Clinical Neurology

Keywords

Genetics
LRRK2
Mutation
Parkinson's disease

Access to Document

10.1002/mds.21233

Cite this

Nichols, W. C., Marek, D. K., Pauciulo, M. W., Pankratz, N., Halter, C. A., Rudolph, A., Shults, C. W., Wojcieszek, J., Foroud, T., Shults, C., Marshall, F., Oakes, D., Rudolph, A., Shinaman, A., Marder, K., Conneally, P. M., Halter, C., Lyons, K., Siemers, E., ... Julian-Baros, E. (2007). R1514Q substitution in Lrrk2 is not a pathogenic Parkinson's disease mutation. Movement Disorders, 22(2), 254-256. https://doi.org/10.1002/mds.21233

@article{f8319004992c48899b8292cd4866fb29,

title = "R1514Q substitution in Lrrk2 is not a pathogenic Parkinson's disease mutation",

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.",

keywords = "Genetics, LRRK2, Mutation, Parkinson's disease",

author = "Nichols, {William C.} and Marek, {Diane K.} and Pauciulo, {Michael W.} and Nathan Pankratz and Halter, {Cheryl A.} and Alice Rudolph and Shults, {Clifford W.} and Joanne Wojcieszek and Tatiana Foroud and C. Shults and F. Marshall and D. Oakes and A. Rudolph and A. Shinaman and K. Marder and Conneally, {P. M.} and C. Halter and K. Lyons and E. Siemers and S. Factor and D. Higgins and S. Evans and H. Shill and M. Stacy and J. Danielson and L. Marlor and K. Williamson and J. Jankovic and C. Hunter and D. Simon and P. Ryan and L. Scollins and R. Saunders-Pullman and K. Boyar and C. Costan-Toth and E. Ohmann and L. Sudarsky and C. Joubert and J. Friedman and K. Chou and H. Fernandez and M. Lannon and N. Galvez-Jimenez and A. Podichetty and P. Lewitt and M. DeAngelis and C. O'Brien and L. Seeberger and C. Dingmann and D. Judd and K. Marder and J. Fraser and J. Harris and J. Bertoni and C. Peterson and S. Chouinard and M. Panisset and J. Hall and H. Poiffaut and V. Calabrese and P. Roberge and J. Wojcieszek and J. Belden and C. Halter and D. Jennings and K. Marek and S. Mendick and S. Reich and B. Dunlop and M. Jog and C. Horn and J. Rao and M. Cook and R. Uitti and M. Turk and T. Ajax and J. Mannetter and M. Panisset and J. Hall and K. Sethi and J. Carpenter and K. Ligon and S. Narayan and L. Woodward and K. Blindauer and J. Petit and L. Elmer and E. Aiken and K. Davis and C. Schell and S. Wilson and M. Velickovic and W. Koller and S. Phipps and A. Feigin and M. Gordon and J. Hamann and E. Licari and M. Marotta-Kollarus and B. Shannon and R. Winnick and T. Simuni and A. Kaczmarek and K. Williams and M. Wolff and M. Fernandez and J. Hubble and S. Kostyk and A. Campbell and C. Reider and R. Camicioli and J. Carter and P. Andrews and S. Morehouse and C. Stone and T. Mendis and D. Grimes and P. Gray and K. Haas and J. Sutton and B. Hutchinson and J. Young and A. Rajput and A. Rajput and L. Klassen and T. Shirley and B. Manyam and P. Simpson and J. Whetteckey and B. Wulbrecht and D. Truong and M. Pathak and N. Luong and T. Tra and A. Tran and J. Vo and A. Lang and G. Kleiner-Fisman and A. Nieves and J. So and G. Podskalny and L. Giffin and P. Atchison and C. Allen and W. Martin and M. Wieler and O. Suchowersky and M. Klimek and N. Hermanowicz and S. Niswonger and C. Shults and D. Fontaine and M. Aminoff and C. Christine and M. Diminno and J. Hevezi and A. Dalvi and U. Kang and J. Richman and S. Uy and J. Young and A. Dalvi and A. Sahay and D. Schwieterman and M. Leehey and S. Culver and T. Derian and T. Demarcaida and S. Belber and R. Rodnitzky and J. Dobson and R. Pahwa and K. Lyons and T. Gales and S. Thomas and L. Shulman and W. Weiner and K. Dustin and C. Singer and W. Koller and K. Lyons and W. Weiner and L. Zelaya and P. Tuite and V. Hagen and S. Rolandelli and R. Schacherer and P. Gordon and J. Werner and C. Serrano and S. Roque and R. Kurlan and D. Berry and I. Gardiner and R. Hauser and J. Sanchez-Ramos and T. Zesiewicz and H. Delgado and K. Price and P. Rodriguez and R. Pfeiffer and L. Davis and B. Pfeiffer and R. Dewey and B. Hayward and M. Meacham and F. Walker and V. Hunt and B. Racette and L. Good and M. Rundle and A. Watts and A. Wang and T. Ross and S. Bennett and D. Kamp and E. Julian-Baros",

year = "2007",

month = jan,

day = "15",

doi = "10.1002/mds.21233",

language = "English (US)",

volume = "22",

pages = "254--256",

journal = "Movement Disorders",

issn = "0885-3185",

publisher = "John Wiley and Sons Inc.",

number = "2",

}

Nichols, WC, Marek, DK, Pauciulo, MW, Pankratz, N, Halter, CA, Rudolph, A, Shults, CW, Wojcieszek, J, Foroud, T, Shults, C, Marshall, F, Oakes, D, Rudolph, A, Shinaman, A, Marder, K, Conneally, PM, 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 2007, 'R1514Q substitution in Lrrk2 is not a pathogenic Parkinson's disease mutation', Movement Disorders, vol. 22, no. 2, pp. 254-256. https://doi.org/10.1002/mds.21233

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 - 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 - 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.

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

SN - 0885-3185

VL - 22

SP - 254

EP - 256

JO - Movement Disorders

JF - Movement Disorders

IS - 2

ER -

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

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