Translation Initiator EIF4G1 Mutations in Familial Parkinson Disease

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

doi:10.1016/j.ajhg.2011.08.009

Cited by 257 publications

(201 citation statements)

References 27 publications

Supporting

Mentioning

192

Contrasting

Unclassified

Order By: Relevance

“…As previously reported (Chartier-Harlin et al, 2011), no significant association with PD was found. Our cases with p.G686C mutations had idiopathic PD, good responses to L-DOPA and no dementia, consistent with the late-onset idiopathic Lewy body parkinsonism previously reported in EIF4G1 patient carriers.…”

Section: Discussionsupporting

confidence: 62%

“…Linkage and candidate gene analysis identified the p.R1205H mutation in EIF4G1, encoding a component of the eIF4F translation initiation complex that regulates cell survival in response to stressors, in a large French family with AD late-onset PD and seven smaller families of various origins, probably resulting from an ancestral founder (Chartier-Harlin et al, 2011). Screening additional patients with parkinsonism and Lewy body disease identified four less frequent putatively disease-causing mutations, p.A502V, p.G686C, p.S1164R and p.R1197W, absent from ~4,000 controls, but their involvement in disease pathogenesis remains inconclusive, in absence of segregation analyses.…”

Section: Discussionmentioning

confidence: 99%

“…Peripheral blood was collected, with written informed consent, and DNA extracted from leukocytes by standard procedures. The 31 EIF4G1 coding exons and exon-intron junctions were sequenced as reported, with modifications (Chartier-Harlin et al, 2011 Male patient FPD-832-1 carried LRRK2 p.G2019S in addition to EIF4G1 p.G686C.…”

Section: Molecular Methodsmentioning

confidence: 99%

“…Two other genes [Leucine-rich repeat kinase 2 (LRRK2)/PARK8 and vacuolar protein sorting 35 ortholog (VPS35)] were since conclusively associated with autosomal dominant (AD) and four [parkin/PARK2, PTEN-induced kinase 1 (PINK1)/PARK6, DJ-1/PARK7, ATP13A2/PARK9] with early-onset autosomal recessive (AR) PD (Corti et al, 2011;Vilariño-Güell et al, 2011;Zimprich et al, 2011). Recently, mutations in eukaryotic translation initiation factor 4-gamma (EIF4G1)/PARK18 was reported as a probable cause of AD late-onset PD (Chartier-Harlin et al, 2011). Here, to 4/Lesage/NBA-12-215 4 determine the frequency and pathogenicity of EIF4G1 variants, we screened all 31 EIF4G1 coding exons in a series of AD PD patients and matched controls.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

EIF4G1 in familial Parkinson's disease: pathogenic mutations or rare benign variants?

Lesage

Condroyer

Klebe

et al. 2012

Neurobiology of Aging

View full text Add to dashboard Cite

Mutations in the eukaryotic translation initiation factor 4-gamma (EIF4G1) gene, encoding a component of the eIF4F translation initiation complex, were recently reported as a possible cause for the autosomal dominant form of Parkinson's disease (PD). Here, we describe the screening of all 31 EIF4G1 coding exons in a series of 251 index cases with autosomal dominant PD, mostly of French origin and in 236 European control subjects. We identified 12 rare coding variants (either nonsynonymous amino acid substitutions or in frame deletions/insertions), including 6 variants present only in cases and 3 in controls. Segregation was possible only for 1 variant (p.E462delInsGK) that was found in 2 affected siblings. In addition, we found 2 previously reported pathogenic variants in 2 isolated patients (p.G686C) and in a control subject (p.R1197W). These data do not support the pathogenicity of several EIF4G1 variants in PD, at least in the French population

show abstract

Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Section: Molecular Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

EIF4G1 in familial Parkinson's disease: pathogenic mutations or rare benign variants?

Lesage

Condroyer

Klebe

et al. 2012

Neurobiology of Aging

View full text Add to dashboard Cite

show abstract

“…All novel variants were examined for disease segregation in affected and unaffected family members by additional sequencing. Evidence for segregation with disease was assessed using parametric linkage analysis, as previously described (2). All potentially pathogenic mutations were genotyped in case -control series using TaqMan probes; and mutations carriers confirmed by direct sequencing.…”

Section: Sequencing and Genotyping Analysismentioning

confidence: 99%

DNAJC13 mutations in Parkinson disease

Vilariño‐Güell

Rajput

Milnerwood

et al. 2013

Human Molecular Genetics

Self Cite

274

229

View full text Add to dashboard Cite

A Saskatchewan multi-incident family was clinically characterized with Parkinson disease (PD) and Lewy body pathology. PD segregates as an autosomal-dominant trait, which could not be ascribed to any known mutation. DNA from three affected members was subjected to exome sequencing. Genome alignment, variant annotation and comparative analyses were used to identify shared coding mutations. Sanger sequencing was performed within the extended family and ethnically matched controls. Subsequent genotyping was performed in a multi-ethnic case–control series consisting of 2928 patients and 2676 control subjects from Canada, Norway, Taiwan, Tunisia, and the USA. A novel mutation in receptor-mediated endocytosis 8/RME-8 (DNAJC13 p.Asn855Ser) was found to segregate with disease. Screening of cases and controls identified four additional patients with the mutation, of which two had familial parkinsonism. All carriers shared an ancestral DNAJC13 p.Asn855Ser haplotype and claimed Dutch–German–Russian Mennonite heritage. DNAJC13 regulates the dynamics of clathrin coats on early endosomes. Cellular analysis shows that the mutation confers a toxic gain-of-function and impairs endosomal transport. DNAJC13 immunoreactivity was also noted within Lewy body inclusions. In late-onset disease which is most reminiscent of idiopathic PD subtle deficits in endosomal receptor-sorting/recycling are highlighted by the discovery of pathogenic mutations VPS35, LRRK2 and now DNAJC13. With this latest discovery, and from a neuronal perspective, a temporal and functional ecology is emerging that connects synaptic exo- and endocytosis, vesicular trafficking, endosomal recycling and the endo-lysosomal degradative pathway. Molecular deficits in these processes are genetically linked to the phenotypic spectrum of parkinsonism associated with Lewy body pathology.

show abstract

F-Box Only Protein 7 Gene in Parkinsonian-Pyramidal Disease

Deng¹,

Liu²,

Jankovic³

2012

JAMA Neurol

View full text Add to dashboard Cite

arkinson disease is one of the most common neurodegenerative diseases associated with aging. At least 18 genetic loci and 13 disease-related genes for parkinsonism have been identified. Among them, PARK15-associated parkinsonism, also referred to as parkinsonianpyramidal disease (PPD), was found to be caused by mutations in the F-box only protein 7 gene (FBXO7). Parkinsonian-pyramidal disease differs from typical Parkinson disease chiefly by juvenile onset and the presence of spasticity. Four mutations have been identified and a pattern of autosomal recessive inheritance has been proposed in all reported PPD families. The FBXO7 protein is a member of the Skp1-Cullin-F-box-type E3 ubiquitin ligases, which play important roles in targeting proteins for ubiquitination. Although PPD is a relatively rare parkinsonian disorder, understanding its genetic and pathological mechanisms may lead to new insights into the pathogenesis of Parkinson disease and development of therapeutic strategies not only for PPD but also for other parkinsonian disorders.

show abstract

Translation Initiator EIF4G1 Mutations in Familial Parkinson Disease

Cited by 257 publications

References 27 publications

EIF4G1 in familial Parkinson's disease: pathogenic mutations or rare benign variants?

EIF4G1 in familial Parkinson's disease: pathogenic mutations or rare benign variants?

DNAJC13 mutations in Parkinson disease

F-Box Only Protein 7 Gene in Parkinsonian-Pyramidal Disease

Contact Info

Product

Resources

About