Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease

Tatiana Foroud, S. K. Uniacke, L. Liu, N. Pankratz, A. Rudolph, C. Halter, C. Shults, K. Marder, P. M. Conneally, W. C. Nichols, Lawrence Golbe, William Koller, Kelly Lyons, Frederick Marshall, David Oakes, Aileen Shinaman, Eric Siemers, Joanne Wojcieszek, Joann Belden, Julie CarterRichard Camicioli, Pamela Andrews, Magali Fernandez, Jean Hubble, Carson Reider, Ali Rajput, Alex Rajput, Theresa Shirley, Michael Panisset, Jean Hall, Tilak Mendis, David A. Grimes, Peggy Gray, Carmen Serrano Ramos, Sandra Roque, Stephen Reich, Becky Dunlop, Robert Hauser, Juan Sanchez-Ramos, Theresa Zesiewicz, Holly Delgado, Joseph Friedman, Hubert Fernandez, Margaret Lannon, Lauren Seeberger, Christopher O'Brien, Deborah Judd, Lawrence Elmer, Kathy Davis, Deborah Fontaine, Ronald Pfeiffer, Brenda Pfeiffer, Michael Aminoff, Mariann DiMinno, Daniel Truong, Mayank Pathak, Anhoa Tran, Robert Rodnitzky, Judith Dobson, Rajesh Pahwa, Stephanie Thomas, Danna Jennings, Kenneth Marek, Susan Mendick, Juliette Harris, William Weiner, Roger Kurlan, Debra Berry, Peter Lewitt, Maryan DeAngelis, Paul Tuite, Robyn Schacherer, Wayne Martin, Marguerite Wieler, Bala Manyam, Patricia Simpson, John Bertoni, Carolyn Peterson, Mark F. Gordon, Joanna Hamann, Joseph Jankovic, Christine Hunter, Stewart Factor, Sharon Evans, Anette Nieves, Julie So, Mark Stacy, Kelli Williamson, Francis Walker, Victoria Hunt, Un Jung Kang, Shirley Uy, Karen Bindauer, Jeannine Petit, David Simon, Lisa Scollins, Rachel Saunders Pullman, Karyn Boyer, Paul Gordon

Research output: Contribution to journalArticle

174 Citations (Scopus)

Abstract

Background: The vast majority of the parkin mutations previously identified have been found in individuals with juvenile or early onset PD. Previous screening of later onset PD cohorts has not identified substantial numbers of parkin mutations. Methods: Families with at least two siblings with PD were ascertained to identify genes contributing to PD susceptibility. Screening of the parkin gene, by both quantitative PCR and exon sequencing, was performed in those families with either early onset PD (age onset ≤550 years) or positive lod score with a marker in intron 7 of the parkin gene. Results: A total of 25 different mutations in the parkin gene were identified in 103 individuals from 47 families. Mutations were found in both parkin alleles in 41 of the individuals, whereas a single mutation in only one of the two parkin alleles was observed in 62 individuals. Thirty-five of the subjects (34%) with a parkin mutation had an age at onset of 60 years or above with 30 of these 35 (86%) having a detectable mutation on only one parkin allele. Few significant clinical differences were observed among the individuals with two, one, or no mutated copies of the parkin gene. Conclusions: Mutations in the parkin gene occur among individuals with PD with an older age at onset (≥60 years) who have a positive family history of the disease. In addition, the clinical findings of parkin-positive individuals are remarkably similar to those without mutations.

Original languageEnglish (US)
Pages (from-to)796-801
Number of pages6
JournalNeurology
Volume60
Issue number5
DOIs
StatePublished - Mar 11 2003

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Parkinson Disease
Mutation
Genes
Age of Onset
Alleles
Lod Score
Late Onset Disorders
Introns
Exons
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Foroud, T., Uniacke, S. K., Liu, L., Pankratz, N., Rudolph, A., Halter, C., ... Gordon, P. (2003). Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease. Neurology, 60(5), 796-801. https://doi.org/10.1212/01.WNL.0000049470.00180.07

Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease. / Foroud, Tatiana; Uniacke, S. K.; Liu, L.; Pankratz, N.; Rudolph, A.; Halter, C.; Shults, C.; Marder, K.; Conneally, P. M.; Nichols, W. C.; Golbe, Lawrence; Koller, William; Lyons, Kelly; Marshall, Frederick; Oakes, David; Shinaman, Aileen; Siemers, Eric; Wojcieszek, Joanne; Belden, Joann; Carter, Julie; Camicioli, Richard; Andrews, Pamela; Fernandez, Magali; Hubble, Jean; Reider, Carson; Rajput, Ali; Rajput, Alex; Shirley, Theresa; Panisset, Michael; Hall, Jean; Mendis, Tilak; Grimes, David A.; Gray, Peggy; Serrano Ramos, Carmen; Roque, Sandra; Reich, Stephen; Dunlop, Becky; Hauser, Robert; Sanchez-Ramos, Juan; Zesiewicz, Theresa; Delgado, Holly; Friedman, Joseph; Fernandez, Hubert; Lannon, Margaret; Seeberger, Lauren; O'Brien, Christopher; Judd, Deborah; Elmer, Lawrence; Davis, Kathy; Fontaine, Deborah; Pfeiffer, Ronald; Pfeiffer, Brenda; Aminoff, Michael; DiMinno, Mariann; Truong, Daniel; Pathak, Mayank; Tran, Anhoa; Rodnitzky, Robert; Dobson, Judith; Pahwa, Rajesh; Thomas, Stephanie; Jennings, Danna; Marek, Kenneth; Mendick, Susan; Harris, Juliette; Weiner, William; Kurlan, Roger; Berry, Debra; Lewitt, Peter; DeAngelis, Maryan; Tuite, Paul; Schacherer, Robyn; Martin, Wayne; Wieler, Marguerite; Manyam, Bala; Simpson, Patricia; Bertoni, John; Peterson, Carolyn; Gordon, Mark F.; Hamann, Joanna; Jankovic, Joseph; Hunter, Christine; Factor, Stewart; Evans, Sharon; Nieves, Anette; So, Julie; Stacy, Mark; Williamson, Kelli; Walker, Francis; Hunt, Victoria; Kang, Un Jung; Uy, Shirley; Bindauer, Karen; Petit, Jeannine; Simon, David; Scollins, Lisa; Pullman, Rachel Saunders; Boyer, Karyn; Gordon, Paul.

In: Neurology, Vol. 60, No. 5, 11.03.2003, p. 796-801.

Research output: Contribution to journalArticle

Foroud, T, Uniacke, SK, Liu, L, Pankratz, N, Rudolph, A, Halter, C, Shults, C, Marder, K, Conneally, PM, Nichols, WC, Golbe, L, Koller, W, Lyons, K, Marshall, F, Oakes, D, Shinaman, A, Siemers, E, Wojcieszek, J, Belden, J, Carter, J, Camicioli, R, Andrews, P, Fernandez, M, Hubble, J, Reider, C, Rajput, A, Rajput, A, Shirley, T, Panisset, M, Hall, J, Mendis, T, Grimes, DA, Gray, P, Serrano Ramos, C, Roque, S, Reich, S, Dunlop, B, Hauser, R, Sanchez-Ramos, J, Zesiewicz, T, Delgado, H, Friedman, J, Fernandez, H, Lannon, M, Seeberger, L, O'Brien, C, Judd, D, Elmer, L, Davis, K, Fontaine, D, Pfeiffer, R, Pfeiffer, B, Aminoff, M, DiMinno, M, Truong, D, Pathak, M, Tran, A, Rodnitzky, R, Dobson, J, Pahwa, R, Thomas, S, Jennings, D, Marek, K, Mendick, S, Harris, J, Weiner, W, Kurlan, R, Berry, D, Lewitt, P, DeAngelis, M, Tuite, P, Schacherer, R, Martin, W, Wieler, M, Manyam, B, Simpson, P, Bertoni, J, Peterson, C, Gordon, MF, Hamann, J, Jankovic, J, Hunter, C, Factor, S, Evans, S, Nieves, A, So, J, Stacy, M, Williamson, K, Walker, F, Hunt, V, Kang, UJ, Uy, S, Bindauer, K, Petit, J, Simon, D, Scollins, L, Pullman, RS, Boyer, K & Gordon, P 2003, 'Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease', Neurology, vol. 60, no. 5, pp. 796-801. https://doi.org/10.1212/01.WNL.0000049470.00180.07
Foroud T, Uniacke SK, Liu L, Pankratz N, Rudolph A, Halter C et al. Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease. Neurology. 2003 Mar 11;60(5):796-801. https://doi.org/10.1212/01.WNL.0000049470.00180.07
Foroud, Tatiana ; Uniacke, S. K. ; Liu, L. ; Pankratz, N. ; Rudolph, A. ; Halter, C. ; Shults, C. ; Marder, K. ; Conneally, P. M. ; Nichols, W. C. ; Golbe, Lawrence ; Koller, William ; Lyons, Kelly ; Marshall, Frederick ; Oakes, David ; Shinaman, Aileen ; Siemers, Eric ; Wojcieszek, Joanne ; Belden, Joann ; Carter, Julie ; Camicioli, Richard ; Andrews, Pamela ; Fernandez, Magali ; Hubble, Jean ; Reider, Carson ; Rajput, Ali ; Rajput, Alex ; Shirley, Theresa ; Panisset, Michael ; Hall, Jean ; Mendis, Tilak ; Grimes, David A. ; Gray, Peggy ; Serrano Ramos, Carmen ; Roque, Sandra ; Reich, Stephen ; Dunlop, Becky ; Hauser, Robert ; Sanchez-Ramos, Juan ; Zesiewicz, Theresa ; Delgado, Holly ; Friedman, Joseph ; Fernandez, Hubert ; Lannon, Margaret ; Seeberger, Lauren ; O'Brien, Christopher ; Judd, Deborah ; Elmer, Lawrence ; Davis, Kathy ; Fontaine, Deborah ; Pfeiffer, Ronald ; Pfeiffer, Brenda ; Aminoff, Michael ; DiMinno, Mariann ; Truong, Daniel ; Pathak, Mayank ; Tran, Anhoa ; Rodnitzky, Robert ; Dobson, Judith ; Pahwa, Rajesh ; Thomas, Stephanie ; Jennings, Danna ; Marek, Kenneth ; Mendick, Susan ; Harris, Juliette ; Weiner, William ; Kurlan, Roger ; Berry, Debra ; Lewitt, Peter ; DeAngelis, Maryan ; Tuite, Paul ; Schacherer, Robyn ; Martin, Wayne ; Wieler, Marguerite ; Manyam, Bala ; Simpson, Patricia ; Bertoni, John ; Peterson, Carolyn ; Gordon, Mark F. ; Hamann, Joanna ; Jankovic, Joseph ; Hunter, Christine ; Factor, Stewart ; Evans, Sharon ; Nieves, Anette ; So, Julie ; Stacy, Mark ; Williamson, Kelli ; Walker, Francis ; Hunt, Victoria ; Kang, Un Jung ; Uy, Shirley ; Bindauer, Karen ; Petit, Jeannine ; Simon, David ; Scollins, Lisa ; Pullman, Rachel Saunders ; Boyer, Karyn ; Gordon, Paul. / Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease. In: Neurology. 2003 ; Vol. 60, No. 5. pp. 796-801.
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title = "Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease",
abstract = "Background: The vast majority of the parkin mutations previously identified have been found in individuals with juvenile or early onset PD. Previous screening of later onset PD cohorts has not identified substantial numbers of parkin mutations. Methods: Families with at least two siblings with PD were ascertained to identify genes contributing to PD susceptibility. Screening of the parkin gene, by both quantitative PCR and exon sequencing, was performed in those families with either early onset PD (age onset ≤550 years) or positive lod score with a marker in intron 7 of the parkin gene. Results: A total of 25 different mutations in the parkin gene were identified in 103 individuals from 47 families. Mutations were found in both parkin alleles in 41 of the individuals, whereas a single mutation in only one of the two parkin alleles was observed in 62 individuals. Thirty-five of the subjects (34{\%}) with a parkin mutation had an age at onset of 60 years or above with 30 of these 35 (86{\%}) having a detectable mutation on only one parkin allele. Few significant clinical differences were observed among the individuals with two, one, or no mutated copies of the parkin gene. Conclusions: Mutations in the parkin gene occur among individuals with PD with an older age at onset (≥60 years) who have a positive family history of the disease. In addition, the clinical findings of parkin-positive individuals are remarkably similar to those without mutations.",
author = "Tatiana Foroud and Uniacke, {S. K.} and L. Liu and N. Pankratz and A. Rudolph and C. Halter and C. Shults and K. Marder and Conneally, {P. M.} and Nichols, {W. C.} and Lawrence Golbe and William Koller and Kelly Lyons and Frederick Marshall and David Oakes and Aileen Shinaman and Eric Siemers and Joanne Wojcieszek and Joann Belden and Julie Carter and Richard Camicioli and Pamela Andrews and Magali Fernandez and Jean Hubble and Carson Reider and Ali Rajput and Alex Rajput and Theresa Shirley and Michael Panisset and Jean Hall and Tilak Mendis and Grimes, {David A.} and Peggy Gray and {Serrano Ramos}, Carmen and Sandra Roque and Stephen Reich and Becky Dunlop and Robert Hauser and Juan Sanchez-Ramos and Theresa Zesiewicz and Holly Delgado and Joseph Friedman and Hubert Fernandez and Margaret Lannon and Lauren Seeberger and Christopher O'Brien and Deborah Judd and Lawrence Elmer and Kathy Davis and Deborah Fontaine and Ronald Pfeiffer and Brenda Pfeiffer and Michael Aminoff and Mariann DiMinno and Daniel Truong and Mayank Pathak and Anhoa Tran and Robert Rodnitzky and Judith Dobson and Rajesh Pahwa and Stephanie Thomas and Danna Jennings and Kenneth Marek and Susan Mendick and Juliette Harris and William Weiner and Roger Kurlan and Debra Berry and Peter Lewitt and Maryan DeAngelis and Paul Tuite and Robyn Schacherer and Wayne Martin and Marguerite Wieler and Bala Manyam and Patricia Simpson and John Bertoni and Carolyn Peterson and Gordon, {Mark F.} and Joanna Hamann and Joseph Jankovic and Christine Hunter and Stewart Factor and Sharon Evans and Anette Nieves and Julie So and Mark Stacy and Kelli Williamson and Francis Walker and Victoria Hunt and Kang, {Un Jung} and Shirley Uy and Karen Bindauer and Jeannine Petit and David Simon and Lisa Scollins and Pullman, {Rachel Saunders} and Karyn Boyer and Paul Gordon",
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TY - JOUR

T1 - Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease

AU - Foroud, Tatiana

AU - Uniacke, S. K.

AU - Liu, L.

AU - Pankratz, N.

AU - Rudolph, A.

AU - Halter, C.

AU - Shults, C.

AU - Marder, K.

AU - Conneally, P. M.

AU - Nichols, W. C.

AU - Golbe, Lawrence

AU - Koller, William

AU - Lyons, Kelly

AU - Marshall, Frederick

AU - Oakes, David

AU - Shinaman, Aileen

AU - Siemers, Eric

AU - Wojcieszek, Joanne

AU - Belden, Joann

AU - Carter, Julie

AU - Camicioli, Richard

AU - Andrews, Pamela

AU - Fernandez, Magali

AU - Hubble, Jean

AU - Reider, Carson

AU - Rajput, Ali

AU - Rajput, Alex

AU - Shirley, Theresa

AU - Panisset, Michael

AU - Hall, Jean

AU - Mendis, Tilak

AU - Grimes, David A.

AU - Gray, Peggy

AU - Serrano Ramos, Carmen

AU - Roque, Sandra

AU - Reich, Stephen

AU - Dunlop, Becky

AU - Hauser, Robert

AU - Sanchez-Ramos, Juan

AU - Zesiewicz, Theresa

AU - Delgado, Holly

AU - Friedman, Joseph

AU - Fernandez, Hubert

AU - Lannon, Margaret

AU - Seeberger, Lauren

AU - O'Brien, Christopher

AU - Judd, Deborah

AU - Elmer, Lawrence

AU - Davis, Kathy

AU - Fontaine, Deborah

AU - Pfeiffer, Ronald

AU - Pfeiffer, Brenda

AU - Aminoff, Michael

AU - DiMinno, Mariann

AU - Truong, Daniel

AU - Pathak, Mayank

AU - Tran, Anhoa

AU - Rodnitzky, Robert

AU - Dobson, Judith

AU - Pahwa, Rajesh

AU - Thomas, Stephanie

AU - Jennings, Danna

AU - Marek, Kenneth

AU - Mendick, Susan

AU - Harris, Juliette

AU - Weiner, William

AU - Kurlan, Roger

AU - Berry, Debra

AU - Lewitt, Peter

AU - DeAngelis, Maryan

AU - Tuite, Paul

AU - Schacherer, Robyn

AU - Martin, Wayne

AU - Wieler, Marguerite

AU - Manyam, Bala

AU - Simpson, Patricia

AU - Bertoni, John

AU - Peterson, Carolyn

AU - Gordon, Mark F.

AU - Hamann, Joanna

AU - Jankovic, Joseph

AU - Hunter, Christine

AU - Factor, Stewart

AU - Evans, Sharon

AU - Nieves, Anette

AU - So, Julie

AU - Stacy, Mark

AU - Williamson, Kelli

AU - Walker, Francis

AU - Hunt, Victoria

AU - Kang, Un Jung

AU - Uy, Shirley

AU - Bindauer, Karen

AU - Petit, Jeannine

AU - Simon, David

AU - Scollins, Lisa

AU - Pullman, Rachel Saunders

AU - Boyer, Karyn

AU - Gordon, Paul

PY - 2003/3/11

Y1 - 2003/3/11

N2 - Background: The vast majority of the parkin mutations previously identified have been found in individuals with juvenile or early onset PD. Previous screening of later onset PD cohorts has not identified substantial numbers of parkin mutations. Methods: Families with at least two siblings with PD were ascertained to identify genes contributing to PD susceptibility. Screening of the parkin gene, by both quantitative PCR and exon sequencing, was performed in those families with either early onset PD (age onset ≤550 years) or positive lod score with a marker in intron 7 of the parkin gene. Results: A total of 25 different mutations in the parkin gene were identified in 103 individuals from 47 families. Mutations were found in both parkin alleles in 41 of the individuals, whereas a single mutation in only one of the two parkin alleles was observed in 62 individuals. Thirty-five of the subjects (34%) with a parkin mutation had an age at onset of 60 years or above with 30 of these 35 (86%) having a detectable mutation on only one parkin allele. Few significant clinical differences were observed among the individuals with two, one, or no mutated copies of the parkin gene. Conclusions: Mutations in the parkin gene occur among individuals with PD with an older age at onset (≥60 years) who have a positive family history of the disease. In addition, the clinical findings of parkin-positive individuals are remarkably similar to those without mutations.

AB - Background: The vast majority of the parkin mutations previously identified have been found in individuals with juvenile or early onset PD. Previous screening of later onset PD cohorts has not identified substantial numbers of parkin mutations. Methods: Families with at least two siblings with PD were ascertained to identify genes contributing to PD susceptibility. Screening of the parkin gene, by both quantitative PCR and exon sequencing, was performed in those families with either early onset PD (age onset ≤550 years) or positive lod score with a marker in intron 7 of the parkin gene. Results: A total of 25 different mutations in the parkin gene were identified in 103 individuals from 47 families. Mutations were found in both parkin alleles in 41 of the individuals, whereas a single mutation in only one of the two parkin alleles was observed in 62 individuals. Thirty-five of the subjects (34%) with a parkin mutation had an age at onset of 60 years or above with 30 of these 35 (86%) having a detectable mutation on only one parkin allele. Few significant clinical differences were observed among the individuals with two, one, or no mutated copies of the parkin gene. Conclusions: Mutations in the parkin gene occur among individuals with PD with an older age at onset (≥60 years) who have a positive family history of the disease. In addition, the clinical findings of parkin-positive individuals are remarkably similar to those without mutations.

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