Translation initiator EIF4G1 mutations in familial parkinson disease

Marie Christine Chartier-Harlin; Justus C. Dachsel; Carles Vilariño-Güell; Sarah J. Lincoln; Frédéric Leprêtre; Mary M. Hulihan; Jennifer Kachergus; Austen J. Milnerwood; Lucia Tapia; Mee Sook Song; Emilie Le Rhun; Eugénie Mutez; Lydie Larvor; Aurélie Duflot; Christel Vanbesien-Mailliot; Alexandre Kreisler; Owen A. Ross; Kenya Nishioka; Alexandra I. Soto-Ortolaza; Stephanie A. Cobb; Heather L. Melrose; Bahareh Behrouz; Brett H. Keeling; Justin A. Bacon; Emna Hentati; Lindsey Williams; Akiko Yanagiya; Nahum Sonenberg; Paul J. Lockhart; Abba C. Zubair; Ryan J. Uitti; Jan O. Aasly; Anna Krygowska-Wajs; Grzegorz Opala; Zbigniew K. Wszolek; Roberta Frigerio; Demetrius M. Maraganore; David Gosal; Tim Lynch; Michael Hutchinson; Anna Rita Bentivoglio; Enza Maria Valente; William C. Nichols; Nathan Pankratz; Tatiana Foroud; Rachel A. Gibson; Faycal Hentati; Dennis W. Dickson; Alain Destée; Matthew J. Farrer

doi:10.1016/j.ajhg.2011.08.009

Translation initiator EIF4G1 mutations in familial parkinson disease

Marie Christine Chartier-Harlin, Justus C. Dachsel, Carles Vilariño-Güell, Sarah J. Lincoln, Frédéric Leprêtre, Mary M. Hulihan, Jennifer Kachergus, Austen J. Milnerwood, Lucia Tapia, Mee Sook Song, Emilie Le Rhun, Eugénie Mutez, Lydie Larvor, Aurélie Duflot, Christel Vanbesien-Mailliot, Alexandre Kreisler, Owen A. Ross, Kenya Nishioka, Alexandra I. Soto-Ortolaza, Stephanie A. CobbHeather L. Melrose, Bahareh Behrouz, Brett H. Keeling, Justin A. Bacon, Emna Hentati, Lindsey Williams, Akiko Yanagiya, Nahum Sonenberg, Paul J. Lockhart, Abba C. Zubair, Ryan J. Uitti, Jan O. Aasly, Anna Krygowska-Wajs, Grzegorz Opala, Zbigniew K. Wszolek, Roberta Frigerio, Demetrius M. Maraganore, David Gosal, Tim Lynch, Michael Hutchinson, Anna Rita Bentivoglio, Enza Maria Valente, William C. Nichols, Nathan Pankratz, Tatiana Foroud, Rachel A. Gibson, Faycal Hentati, Dennis W. Dickson, Alain Destée, Matthew J. Farrer

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Abstract

Genome-wide analysis of a multi-incident family with autosomal-dominant parkinsonism has implicated a locus on chromosomal region 3q26-q28. Linkage and disease segregation is explained by a missense mutation c.3614G>A (p.Arg1205His) in eukaryotic translation initiation factor 4-gamma (EIF4G1). Subsequent sequence and genotype analysis identified EIF4G1 c.1505C>T (p.Ala502Val), c.2056G>T (p.Gly686Cys), c.3490A>C (p.Ser1164Arg), c.3589C>T (p.Arg1197Trp) and c.3614G>A (p.Arg1205His) substitutions in affected subjects with familial parkinsonism and idiopathic Lewy body disease but not in control subjects. Despite different countries of origin, persons with EIF4G1 c.1505C>T (p.Ala502Val) or c.3614G>A (p.Arg1205His) mutations appear to share haplotypes consistent with ancestral founders. eIF4G1 p.Ala502Val and p.Arg1205His disrupt eIF4E or eIF3e binding, although the wild-type protein does not, and render mutant cells more vulnerable to reactive oxidative species. EIF4G1 mutations implicate mRNA translation initiation in familial parkinsonism and highlight a convergent pathway for monogenic, toxin and perhaps virally-induced Parkinson disease.

Original language	English (US)
Pages (from-to)	398-406
Number of pages	9
Journal	American journal of human genetics
Volume	89
Issue number	3
DOIs	https://doi.org/10.1016/j.ajhg.2011.08.009
State	Published - Sep 9 2011

ASJC Scopus subject areas

Genetics
Genetics(clinical)

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10.1016/j.ajhg.2011.08.009

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Chartier-Harlin, M. C., Dachsel, J. C., Vilariño-Güell, C., Lincoln, S. J., Leprêtre, F., Hulihan, M. M., Kachergus, J., Milnerwood, A. J., Tapia, L., Song, M. S., Le Rhun, E., Mutez, E., Larvor, L., Duflot, A., Vanbesien-Mailliot, C., Kreisler, A., Ross, O. A., Nishioka, K., Soto-Ortolaza, A. I., ... Farrer, M. J. (2011). Translation initiator EIF4G1 mutations in familial parkinson disease. American journal of human genetics, 89(3), 398-406. https://doi.org/10.1016/j.ajhg.2011.08.009

Chartier-Harlin, MC, Dachsel, JC, Vilariño-Güell, C, Lincoln, SJ, Leprêtre, F, Hulihan, MM, Kachergus, J, Milnerwood, AJ, Tapia, L, Song, MS, Le Rhun, E, Mutez, E, Larvor, L, Duflot, A, Vanbesien-Mailliot, C, Kreisler, A, Ross, OA, Nishioka, K, Soto-Ortolaza, AI, Cobb, SA, Melrose, HL, Behrouz, B, Keeling, BH, Bacon, JA, Hentati, E, Williams, L, Yanagiya, A, Sonenberg, N, Lockhart, PJ, Zubair, AC, Uitti, RJ, Aasly, JO, Krygowska-Wajs, A, Opala, G, Wszolek, ZK, Frigerio, R, Maraganore, DM, Gosal, D, Lynch, T, Hutchinson, M, Bentivoglio, AR, Valente, EM, Nichols, WC, Pankratz, N, Foroud, T, Gibson, RA, Hentati, F, Dickson, DW, Destée, A & Farrer, MJ 2011, 'Translation initiator EIF4G1 mutations in familial parkinson disease', American journal of human genetics, vol. 89, no. 3, pp. 398-406. https://doi.org/10.1016/j.ajhg.2011.08.009

@article{11dfd69b104446768750cc6f3dd2c73e,

title = "Translation initiator EIF4G1 mutations in familial parkinson disease",

abstract = "Genome-wide analysis of a multi-incident family with autosomal-dominant parkinsonism has implicated a locus on chromosomal region 3q26-q28. Linkage and disease segregation is explained by a missense mutation c.3614G>A (p.Arg1205His) in eukaryotic translation initiation factor 4-gamma (EIF4G1). Subsequent sequence and genotype analysis identified EIF4G1 c.1505C>T (p.Ala502Val), c.2056G>T (p.Gly686Cys), c.3490A>C (p.Ser1164Arg), c.3589C>T (p.Arg1197Trp) and c.3614G>A (p.Arg1205His) substitutions in affected subjects with familial parkinsonism and idiopathic Lewy body disease but not in control subjects. Despite different countries of origin, persons with EIF4G1 c.1505C>T (p.Ala502Val) or c.3614G>A (p.Arg1205His) mutations appear to share haplotypes consistent with ancestral founders. eIF4G1 p.Ala502Val and p.Arg1205His disrupt eIF4E or eIF3e binding, although the wild-type protein does not, and render mutant cells more vulnerable to reactive oxidative species. EIF4G1 mutations implicate mRNA translation initiation in familial parkinsonism and highlight a convergent pathway for monogenic, toxin and perhaps virally-induced Parkinson disease.",

author = "Chartier-Harlin, {Marie Christine} and Dachsel, {Justus C.} and Carles Vilari{\~n}o-G{\"u}ell and Lincoln, {Sarah J.} and Fr{\'e}d{\'e}ric Lepr{\^e}tre and Hulihan, {Mary M.} and Jennifer Kachergus and Milnerwood, {Austen J.} and Lucia Tapia and Song, {Mee Sook} and {Le Rhun}, Emilie and Eug{\'e}nie Mutez and Lydie Larvor and Aur{\'e}lie Duflot and Christel Vanbesien-Mailliot and Alexandre Kreisler and Ross, {Owen A.} and Kenya Nishioka and Soto-Ortolaza, {Alexandra I.} and Cobb, {Stephanie A.} and Melrose, {Heather L.} and Bahareh Behrouz and Keeling, {Brett H.} and Bacon, {Justin A.} and Emna Hentati and Lindsey Williams and Akiko Yanagiya and Nahum Sonenberg and Lockhart, {Paul J.} and Zubair, {Abba C.} and Uitti, {Ryan J.} and Aasly, {Jan O.} and Anna Krygowska-Wajs and Grzegorz Opala and Wszolek, {Zbigniew K.} and Roberta Frigerio and Maraganore, {Demetrius M.} and David Gosal and Tim Lynch and Michael Hutchinson and Bentivoglio, {Anna Rita} and Valente, {Enza Maria} and Nichols, {William C.} and Nathan Pankratz and Tatiana Foroud and Gibson, {Rachel A.} and Faycal Hentati and Dickson, {Dennis W.} and Alain Dest{\'e}e and Farrer, {Matthew J.}",

note = "Funding Information: We thank subjects who generously participated in this study. We also thank the many clinicians who have contributed to the follow-up of family P30 over the past 15 years, including Estelle Becquet, Serge Brique, Delphine Prince, Xavier Douay, and Nawal Waucquier. We acknowledge the laboratory support of Clotilde Levecque, Vincent Mouroux, Pierre Semaille, and Trevor Tyson. Studies in France would not have been possible without financial support from CHR de Lille, Universit{\'e} Lille 2, Inserm, French Ministry Hospital Clinical Research Programs (PHRCs) (1994/, 2002/1918, 2005/1914), Association France Parkinson (2005), Fondation de France 2004-013306, 2011-00016815, Fondation de la Recherche M{\'e}dicale (2006), PPF (synucl{\'e}oth{\`e}que 2005-2009), the two Centres de Resources Biologiques (IPL-Lille, CHRU-Lille) and their scientific committee (A.D., M.-C.C.-H., Philippe Amouyel, Florence Pasquier, R{\'e}gis Bordet). Studies in Ireland were supported by the Program for Research in Third Level Institutions (PRTLI). Studies in Italy were supported by the Italian Ministry of Health (Ricerca Corrente 2011, Ricerca Finalizzata, Giovani Ricercatori). Studies in the PROGENI sample were supported by R01NS37167 and the Parkinson Study Group. Clinicogenetic studies in Tunisia were funded in part by the Institute of Neurology, Tunis, and the Michael J. Fox Foundation. GlaxoSmithKline (GSK) funded and provided a subset of the Tunisian case:control samples and associated phenotypic data, and we gratefully acknowledge the PD Programme Team, most notably Tina Stapleton and Carole Stapleton for sample management. We thank James Weber and NIH National Heart, Lung, and Blood Institute/Marshfield Medical Research Foundation for genome-wide genotyping (genotyping award to M.J.F.). Studies performed at Mayo Clinic were financed by NIH National Institute of Neurological Disorders and Stroke (Morris K. Udall Parkinson's Disease Research Center of Excellence; P50 #NS40256 #NS072187; M.J.F., Z.K.W., D.W.D.), 2R01 ES10751 (D.M.M.), the Michael J. Fox Foundation (M.J.F.) and a Herb Geist gift for Lewy body research (M.J.F.). We thank Alice McKinney for supplementary Figure S3. This research was undertaken, in part, thanks to funding from the Canada Excellence Research Chairs program (M.J.F.; C.V.-G.). In addition, Leading Edge Endowment Funds provided by the Province of British Columbia, Life Labs and Genome BC support the Dr. Donald Rix BC Leadership Chair (M.J.F.). The authors (J.O.A., D.W.D., M.J.F., D.M.M.) declare provisional patents relevant to Parkinson's disease, but not to EIF4G1. Royalties have been obtained from licensing related to alpha-synuclein (Alnylam Pharmaceuticals [M.J.F., D.M.M.], Isis Pharmaceuticals [M.J.F.]) and leucine-rich repeat kinase 2 (J.O.A., D.W.D., M.J.F., Z.K.W.) but no conflict of interest is declared. ",

year = "2011",

month = sep,

day = "9",

doi = "10.1016/j.ajhg.2011.08.009",

language = "English (US)",

volume = "89",

pages = "398--406",

journal = "American journal of human genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "3",

}

TY - JOUR

T1 - Translation initiator EIF4G1 mutations in familial parkinson disease

AU - Chartier-Harlin, Marie Christine

AU - Dachsel, Justus C.

AU - Vilariño-Güell, Carles

AU - Lincoln, Sarah J.

AU - Leprêtre, Frédéric

AU - Hulihan, Mary M.

AU - Kachergus, Jennifer

AU - Milnerwood, Austen J.

AU - Tapia, Lucia

AU - Song, Mee Sook

AU - Le Rhun, Emilie

AU - Mutez, Eugénie

AU - Larvor, Lydie

AU - Duflot, Aurélie

AU - Vanbesien-Mailliot, Christel

AU - Kreisler, Alexandre

AU - Ross, Owen A.

AU - Nishioka, Kenya

AU - Soto-Ortolaza, Alexandra I.

AU - Cobb, Stephanie A.

AU - Melrose, Heather L.

AU - Behrouz, Bahareh

AU - Keeling, Brett H.

AU - Bacon, Justin A.

AU - Hentati, Emna

AU - Williams, Lindsey

AU - Yanagiya, Akiko

AU - Sonenberg, Nahum

AU - Lockhart, Paul J.

AU - Zubair, Abba C.

AU - Uitti, Ryan J.

AU - Aasly, Jan O.

AU - Krygowska-Wajs, Anna

AU - Opala, Grzegorz

AU - Wszolek, Zbigniew K.

AU - Frigerio, Roberta

AU - Maraganore, Demetrius M.

AU - Gosal, David

AU - Lynch, Tim

AU - Hutchinson, Michael

AU - Bentivoglio, Anna Rita

AU - Valente, Enza Maria

AU - Nichols, William C.

AU - Pankratz, Nathan

AU - Foroud, Tatiana

AU - Gibson, Rachel A.

AU - Hentati, Faycal

AU - Dickson, Dennis W.

AU - Destée, Alain

AU - Farrer, Matthew J.

N1 - Funding Information: We thank subjects who generously participated in this study. We also thank the many clinicians who have contributed to the follow-up of family P30 over the past 15 years, including Estelle Becquet, Serge Brique, Delphine Prince, Xavier Douay, and Nawal Waucquier. We acknowledge the laboratory support of Clotilde Levecque, Vincent Mouroux, Pierre Semaille, and Trevor Tyson. Studies in France would not have been possible without financial support from CHR de Lille, Université Lille 2, Inserm, French Ministry Hospital Clinical Research Programs (PHRCs) (1994/, 2002/1918, 2005/1914), Association France Parkinson (2005), Fondation de France 2004-013306, 2011-00016815, Fondation de la Recherche Médicale (2006), PPF (synucléothèque 2005-2009), the two Centres de Resources Biologiques (IPL-Lille, CHRU-Lille) and their scientific committee (A.D., M.-C.C.-H., Philippe Amouyel, Florence Pasquier, Régis Bordet). Studies in Ireland were supported by the Program for Research in Third Level Institutions (PRTLI). Studies in Italy were supported by the Italian Ministry of Health (Ricerca Corrente 2011, Ricerca Finalizzata, Giovani Ricercatori). Studies in the PROGENI sample were supported by R01NS37167 and the Parkinson Study Group. Clinicogenetic studies in Tunisia were funded in part by the Institute of Neurology, Tunis, and the Michael J. Fox Foundation. GlaxoSmithKline (GSK) funded and provided a subset of the Tunisian case:control samples and associated phenotypic data, and we gratefully acknowledge the PD Programme Team, most notably Tina Stapleton and Carole Stapleton for sample management. We thank James Weber and NIH National Heart, Lung, and Blood Institute/Marshfield Medical Research Foundation for genome-wide genotyping (genotyping award to M.J.F.). Studies performed at Mayo Clinic were financed by NIH National Institute of Neurological Disorders and Stroke (Morris K. Udall Parkinson's Disease Research Center of Excellence; P50 #NS40256 #NS072187; M.J.F., Z.K.W., D.W.D.), 2R01 ES10751 (D.M.M.), the Michael J. Fox Foundation (M.J.F.) and a Herb Geist gift for Lewy body research (M.J.F.). We thank Alice McKinney for supplementary Figure S3. This research was undertaken, in part, thanks to funding from the Canada Excellence Research Chairs program (M.J.F.; C.V.-G.). In addition, Leading Edge Endowment Funds provided by the Province of British Columbia, Life Labs and Genome BC support the Dr. Donald Rix BC Leadership Chair (M.J.F.). The authors (J.O.A., D.W.D., M.J.F., D.M.M.) declare provisional patents relevant to Parkinson's disease, but not to EIF4G1. Royalties have been obtained from licensing related to alpha-synuclein (Alnylam Pharmaceuticals [M.J.F., D.M.M.], Isis Pharmaceuticals [M.J.F.]) and leucine-rich repeat kinase 2 (J.O.A., D.W.D., M.J.F., Z.K.W.) but no conflict of interest is declared.

PY - 2011/9/9

Y1 - 2011/9/9

N2 - Genome-wide analysis of a multi-incident family with autosomal-dominant parkinsonism has implicated a locus on chromosomal region 3q26-q28. Linkage and disease segregation is explained by a missense mutation c.3614G>A (p.Arg1205His) in eukaryotic translation initiation factor 4-gamma (EIF4G1). Subsequent sequence and genotype analysis identified EIF4G1 c.1505C>T (p.Ala502Val), c.2056G>T (p.Gly686Cys), c.3490A>C (p.Ser1164Arg), c.3589C>T (p.Arg1197Trp) and c.3614G>A (p.Arg1205His) substitutions in affected subjects with familial parkinsonism and idiopathic Lewy body disease but not in control subjects. Despite different countries of origin, persons with EIF4G1 c.1505C>T (p.Ala502Val) or c.3614G>A (p.Arg1205His) mutations appear to share haplotypes consistent with ancestral founders. eIF4G1 p.Ala502Val and p.Arg1205His disrupt eIF4E or eIF3e binding, although the wild-type protein does not, and render mutant cells more vulnerable to reactive oxidative species. EIF4G1 mutations implicate mRNA translation initiation in familial parkinsonism and highlight a convergent pathway for monogenic, toxin and perhaps virally-induced Parkinson disease.

AB - Genome-wide analysis of a multi-incident family with autosomal-dominant parkinsonism has implicated a locus on chromosomal region 3q26-q28. Linkage and disease segregation is explained by a missense mutation c.3614G>A (p.Arg1205His) in eukaryotic translation initiation factor 4-gamma (EIF4G1). Subsequent sequence and genotype analysis identified EIF4G1 c.1505C>T (p.Ala502Val), c.2056G>T (p.Gly686Cys), c.3490A>C (p.Ser1164Arg), c.3589C>T (p.Arg1197Trp) and c.3614G>A (p.Arg1205His) substitutions in affected subjects with familial parkinsonism and idiopathic Lewy body disease but not in control subjects. Despite different countries of origin, persons with EIF4G1 c.1505C>T (p.Ala502Val) or c.3614G>A (p.Arg1205His) mutations appear to share haplotypes consistent with ancestral founders. eIF4G1 p.Ala502Val and p.Arg1205His disrupt eIF4E or eIF3e binding, although the wild-type protein does not, and render mutant cells more vulnerable to reactive oxidative species. EIF4G1 mutations implicate mRNA translation initiation in familial parkinsonism and highlight a convergent pathway for monogenic, toxin and perhaps virally-induced Parkinson disease.

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DO - 10.1016/j.ajhg.2011.08.009

M3 - Article

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AN - SCOPUS:80052780004

SN - 0002-9297

VL - 89

SP - 398

EP - 406

JO - American journal of human genetics

JF - American journal of human genetics

IS - 3

ER -

Translation initiator EIF4G1 mutations in familial parkinson disease

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