Comprehensive Analysis of Familial Parkinsonism Genes in Rapid-Eye-Movement Sleep Behavior Disorder

Kheireddin Mufti; Uladzislau Rudakou; Eric Yu; Lynne Krohn; Jennifer A. Ruskey; Farnaz Asayesh; Sandra B. Laurent; Dan Spiegelman; Isabelle Arnulf; Michele T.M. Hu; Jacques Y. Montplaisir; Jean François Gagnon; Alex Desautels; Yves Dauvilliers; Gian Luigi Gigli; Mariarosaria Valente; Francesco Janes; Birgit Högl; Ambra Stefani; Evi Holzknecht; Karel Šonka; David Kemlink; Wolfgang Oertel; Annette Janzen; Giuseppe Plazzi; Elena Antelmi; Michela Figorilli; Monica Puligheddu; Brit Mollenhauer; Claudia Trenkwalder; Friederike Sixel-Döring; Valérie Cochen De Cock; Christelle Charley Monaca; Anna Heidbreder; Luigi Ferini-Strambi; Femke Dijkstra; Mineke Viaene; Beatriz Abril; Bradley F. Boeve; Ronald B. Postuma; Guy A. Rouleau; Ziv Gan-Or

doi:10.1002/mds.28318

Comprehensive Analysis of Familial Parkinsonism Genes in Rapid-Eye-Movement Sleep Behavior Disorder

Kheireddin Mufti, Uladzislau Rudakou, Eric Yu, Lynne Krohn, Jennifer A. Ruskey, Farnaz Asayesh, Sandra B. Laurent, Dan Spiegelman, Isabelle Arnulf, Michele T.M. Hu, Jacques Y. Montplaisir, Jean François Gagnon, Alex Desautels, Yves Dauvilliers, Gian Luigi Gigli, Mariarosaria Valente, Francesco Janes, Birgit Högl, Ambra Stefani, Evi HolzknechtKarel Šonka, David Kemlink, Wolfgang Oertel, Annette Janzen, Giuseppe Plazzi, Elena Antelmi, Michela Figorilli, Monica Puligheddu, Brit Mollenhauer, Claudia Trenkwalder, Friederike Sixel-Döring, Valérie Cochen De Cock, Christelle Charley Monaca, Anna Heidbreder, Luigi Ferini-Strambi, Femke Dijkstra, Mineke Viaene, Beatriz Abril, Bradley F. Boeve, Ronald B. Postuma, Guy A. Rouleau, Ziv Gan-Or

Neurology

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

Abstract

Background: There is only partial overlap in the genetic background of isolated rapid-eye-movement sleep behavior disorder (iRBD) and Parkinson's disease (PD). Objective: To examine the role of autosomal dominant and recessive PD or atypical parkinsonism genes in the risk of iRBD. Methods: Ten genes, comprising the recessive genes PRKN, DJ-1 (PARK7), PINK1, VPS13C, ATP13A2, FBXO7, and PLA2G6 and the dominant genes LRRK2, GCH1, and VPS35, were fully sequenced in 1039 iRBD patients and 1852 controls of European ancestry, followed by association tests. Results: We found no association between rare heterozygous variants in the tested genes and risk of iRBD. Several homozygous and compound heterozygous carriers were identified, yet there was no overrepresentation in iRBD patients versus controls. Conclusion: Our results do not support a major role for variants in these genes in the risk of iRBD.

Original language	English (US)
Pages (from-to)	235-240
Number of pages	6
Journal	Movement Disorders
Volume	36
Issue number	1
DOIs	https://doi.org/10.1002/mds.28318
State	Published - Jan 2021

Keywords

REM sleep behavior disorder; genetic analysis; Parkinson's disease

ASJC Scopus subject areas

Neurology
Clinical Neurology

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10.1002/mds.28318

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Mufti, K., Rudakou, U., Yu, E., Krohn, L., Ruskey, J. A., Asayesh, F., Laurent, S. B., Spiegelman, D., Arnulf, I., Hu, M. T. M., Montplaisir, J. Y., Gagnon, J. F., Desautels, A., Dauvilliers, Y., Gigli, G. L., Valente, M., Janes, F., Högl, B., Stefani, A., ... Gan-Or, Z. (2021). Comprehensive Analysis of Familial Parkinsonism Genes in Rapid-Eye-Movement Sleep Behavior Disorder. Movement Disorders, 36(1), 235-240. https://doi.org/10.1002/mds.28318

Mufti, K, Rudakou, U, Yu, E, Krohn, L, Ruskey, JA, Asayesh, F, Laurent, SB, Spiegelman, D, Arnulf, I, Hu, MTM, Montplaisir, JY, Gagnon, JF, Desautels, A, Dauvilliers, Y, Gigli, GL, Valente, M, Janes, F, Högl, B, Stefani, A, Holzknecht, E, Šonka, K, Kemlink, D, Oertel, W, Janzen, A, Plazzi, G, Antelmi, E, Figorilli, M, Puligheddu, M, Mollenhauer, B, Trenkwalder, C, Sixel-Döring, F, Cochen De Cock, V, Monaca, CC, Heidbreder, A, Ferini-Strambi, L, Dijkstra, F, Viaene, M, Abril, B, Boeve, BF, Postuma, RB, Rouleau, GA & Gan-Or, Z 2021, 'Comprehensive Analysis of Familial Parkinsonism Genes in Rapid-Eye-Movement Sleep Behavior Disorder', Movement Disorders, vol. 36, no. 1, pp. 235-240. https://doi.org/10.1002/mds.28318

@article{18e7706a7d04434abd82c101ca94de68,

title = "Comprehensive Analysis of Familial Parkinsonism Genes in Rapid-Eye-Movement Sleep Behavior Disorder",

abstract = "Background: There is only partial overlap in the genetic background of isolated rapid-eye-movement sleep behavior disorder (iRBD) and Parkinson's disease (PD). Objective: To examine the role of autosomal dominant and recessive PD or atypical parkinsonism genes in the risk of iRBD. Methods: Ten genes, comprising the recessive genes PRKN, DJ-1 (PARK7), PINK1, VPS13C, ATP13A2, FBXO7, and PLA2G6 and the dominant genes LRRK2, GCH1, and VPS35, were fully sequenced in 1039 iRBD patients and 1852 controls of European ancestry, followed by association tests. Results: We found no association between rare heterozygous variants in the tested genes and risk of iRBD. Several homozygous and compound heterozygous carriers were identified, yet there was no overrepresentation in iRBD patients versus controls. Conclusion: Our results do not support a major role for variants in these genes in the risk of iRBD.",

keywords = "REM sleep behavior disorder; genetic analysis; Parkinson's disease",

author = "Kheireddin Mufti and Uladzislau Rudakou and Eric Yu and Lynne Krohn and Ruskey, {Jennifer A.} and Farnaz Asayesh and Laurent, {Sandra B.} and Dan Spiegelman and Isabelle Arnulf and Hu, {Michele T.M.} and Montplaisir, {Jacques Y.} and Gagnon, {Jean Fran{\c c}ois} and Alex Desautels and Yves Dauvilliers and Gigli, {Gian Luigi} and Mariarosaria Valente and Francesco Janes and Birgit H{\"o}gl and Ambra Stefani and Evi Holzknecht and Karel {\v S}onka and David Kemlink and Wolfgang Oertel and Annette Janzen and Giuseppe Plazzi and Elena Antelmi and Michela Figorilli and Monica Puligheddu and Brit Mollenhauer and Claudia Trenkwalder and Friederike Sixel-D{\"o}ring and {Cochen De Cock}, Val{\'e}rie and Monaca, {Christelle Charley} and Anna Heidbreder and Luigi Ferini-Strambi and Femke Dijkstra and Mineke Viaene and Beatriz Abril and Boeve, {Bradley F.} and Postuma, {Ronald B.} and Rouleau, {Guy A.} and Ziv Gan-Or",

note = "Funding Information: J.‐F.G. holds a Canada Research Chair in cognitive decline in pathological aging. W.O. is Hertie senior research professor, supported by the Hertie Foundation. E.A.F. holds a Canada Research Chair (Tier 1) in PD. G.A.R. holds a Canada Research Chair (Tier 1) in genetics of the nervous system and the Wilder Penfield Chair in neurosciences. Z.G.‐O. is supported by the Fonds de recherche du Qu{\'e}bec–Sant{\'e} Chercheur‐Boursier award and is a Parkinson Canada New Investigator awardee. We thank the participants for their contribution to the study. We thank D. Rochefort, H. Catoire, and V. Zaharieva for their assistance. Funding Information: This work was financially supported by the Michael J. Fox Foundation; the Canadian Consortium on Neurodegeneration in Aging (CCNA); Parkinson Canada; and the Canada First Research Excellence Fund (CFREF), awarded to McGill University for the Healthy Brains for Healthy Lives (HBHL) program. The Montreal cohort was funded by the Canadian Institutes of Health Research (CIHR) and the W. Garfield Weston Foundation. The Oxford Discovery study was funded by the Monument Trust Discovery Award from Parkinson's UK and supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre based at Oxford University Hospitals NHS Trust and University of Oxford, the NIHR Clinical Research Network and the Dementias and Neurodegenerative Diseases Research Network (DeNDRoN). Funding agencies: Funding Information: J.-F.G. holds a Canada Research Chair in cognitive decline in pathological aging. W.O. is Hertie senior research professor, supported by the Hertie Foundation. E.A.F. holds a Canada Research Chair (Tier 1) in PD. G.A.R. holds a Canada Research Chair (Tier 1) in genetics of the nervous system and the Wilder Penfield Chair in neurosciences. Z.G.-O. is supported by the Fonds de recherche du Qu?bec?Sant? Chercheur-Boursier award and is a Parkinson Canada New Investigator awardee. We thank the participants for their contribution to the study. We thank D. Rochefort, H. Catoire, and V. Zaharieva for their assistance. Publisher Copyright: {\textcopyright} 2020 International Parkinson and Movement Disorder Society",

year = "2021",

month = jan,

doi = "10.1002/mds.28318",

language = "English (US)",

volume = "36",

pages = "235--240",

journal = "Movement Disorders",

issn = "0885-3185",

publisher = "John Wiley and Sons Inc.",

number = "1",

}

TY - JOUR

T1 - Comprehensive Analysis of Familial Parkinsonism Genes in Rapid-Eye-Movement Sleep Behavior Disorder

AU - Mufti, Kheireddin

AU - Rudakou, Uladzislau

AU - Yu, Eric

AU - Krohn, Lynne

AU - Ruskey, Jennifer A.

AU - Asayesh, Farnaz

AU - Laurent, Sandra B.

AU - Spiegelman, Dan

AU - Arnulf, Isabelle

AU - Hu, Michele T.M.

AU - Montplaisir, Jacques Y.

AU - Gagnon, Jean François

AU - Desautels, Alex

AU - Dauvilliers, Yves

AU - Gigli, Gian Luigi

AU - Valente, Mariarosaria

AU - Janes, Francesco

AU - Högl, Birgit

AU - Stefani, Ambra

AU - Holzknecht, Evi

AU - Šonka, Karel

AU - Kemlink, David

AU - Oertel, Wolfgang

AU - Janzen, Annette

AU - Plazzi, Giuseppe

AU - Antelmi, Elena

AU - Figorilli, Michela

AU - Puligheddu, Monica

AU - Mollenhauer, Brit

AU - Trenkwalder, Claudia

AU - Sixel-Döring, Friederike

AU - Cochen De Cock, Valérie

AU - Monaca, Christelle Charley

AU - Heidbreder, Anna

AU - Ferini-Strambi, Luigi

AU - Dijkstra, Femke

AU - Viaene, Mineke

AU - Abril, Beatriz

AU - Boeve, Bradley F.

AU - Postuma, Ronald B.

AU - Rouleau, Guy A.

AU - Gan-Or, Ziv

N1 - Funding Information: J.‐F.G. holds a Canada Research Chair in cognitive decline in pathological aging. W.O. is Hertie senior research professor, supported by the Hertie Foundation. E.A.F. holds a Canada Research Chair (Tier 1) in PD. G.A.R. holds a Canada Research Chair (Tier 1) in genetics of the nervous system and the Wilder Penfield Chair in neurosciences. Z.G.‐O. is supported by the Fonds de recherche du Québec–Santé Chercheur‐Boursier award and is a Parkinson Canada New Investigator awardee. We thank the participants for their contribution to the study. We thank D. Rochefort, H. Catoire, and V. Zaharieva for their assistance. Funding Information: This work was financially supported by the Michael J. Fox Foundation; the Canadian Consortium on Neurodegeneration in Aging (CCNA); Parkinson Canada; and the Canada First Research Excellence Fund (CFREF), awarded to McGill University for the Healthy Brains for Healthy Lives (HBHL) program. The Montreal cohort was funded by the Canadian Institutes of Health Research (CIHR) and the W. Garfield Weston Foundation. The Oxford Discovery study was funded by the Monument Trust Discovery Award from Parkinson's UK and supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre based at Oxford University Hospitals NHS Trust and University of Oxford, the NIHR Clinical Research Network and the Dementias and Neurodegenerative Diseases Research Network (DeNDRoN). Funding agencies: Funding Information: J.-F.G. holds a Canada Research Chair in cognitive decline in pathological aging. W.O. is Hertie senior research professor, supported by the Hertie Foundation. E.A.F. holds a Canada Research Chair (Tier 1) in PD. G.A.R. holds a Canada Research Chair (Tier 1) in genetics of the nervous system and the Wilder Penfield Chair in neurosciences. Z.G.-O. is supported by the Fonds de recherche du Qu?bec?Sant? Chercheur-Boursier award and is a Parkinson Canada New Investigator awardee. We thank the participants for their contribution to the study. We thank D. Rochefort, H. Catoire, and V. Zaharieva for their assistance. Publisher Copyright: © 2020 International Parkinson and Movement Disorder Society

PY - 2021/1

Y1 - 2021/1

N2 - Background: There is only partial overlap in the genetic background of isolated rapid-eye-movement sleep behavior disorder (iRBD) and Parkinson's disease (PD). Objective: To examine the role of autosomal dominant and recessive PD or atypical parkinsonism genes in the risk of iRBD. Methods: Ten genes, comprising the recessive genes PRKN, DJ-1 (PARK7), PINK1, VPS13C, ATP13A2, FBXO7, and PLA2G6 and the dominant genes LRRK2, GCH1, and VPS35, were fully sequenced in 1039 iRBD patients and 1852 controls of European ancestry, followed by association tests. Results: We found no association between rare heterozygous variants in the tested genes and risk of iRBD. Several homozygous and compound heterozygous carriers were identified, yet there was no overrepresentation in iRBD patients versus controls. Conclusion: Our results do not support a major role for variants in these genes in the risk of iRBD.

AB - Background: There is only partial overlap in the genetic background of isolated rapid-eye-movement sleep behavior disorder (iRBD) and Parkinson's disease (PD). Objective: To examine the role of autosomal dominant and recessive PD or atypical parkinsonism genes in the risk of iRBD. Methods: Ten genes, comprising the recessive genes PRKN, DJ-1 (PARK7), PINK1, VPS13C, ATP13A2, FBXO7, and PLA2G6 and the dominant genes LRRK2, GCH1, and VPS35, were fully sequenced in 1039 iRBD patients and 1852 controls of European ancestry, followed by association tests. Results: We found no association between rare heterozygous variants in the tested genes and risk of iRBD. Several homozygous and compound heterozygous carriers were identified, yet there was no overrepresentation in iRBD patients versus controls. Conclusion: Our results do not support a major role for variants in these genes in the risk of iRBD.

KW - REM sleep behavior disorder; genetic analysis; Parkinson's disease

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U2 - 10.1002/mds.28318

DO - 10.1002/mds.28318

M3 - Article

C2 - 33001463

AN - SCOPUS:85091797307

SN - 0885-3185

VL - 36

SP - 235

EP - 240

JO - Movement Disorders

JF - Movement Disorders

IS - 1

ER -

Comprehensive Analysis of Familial Parkinsonism Genes in Rapid-Eye-Movement Sleep Behavior Disorder

Abstract

Keywords

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