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@ARTICLE{Lesage:138456,
author = {Lesage, Suzanne and Drouet, Valérie and Majounie, Elisa
and Deramecourt, Vincent and Jacoupy, Maxime and Nicolas,
Aude and Cormier-Dequaire, Florence and Hassoun, Sidi
Mohamed and Pujol, Claire and Ciura, Sorana and
Erpapazoglou, Zoi and Usenko, Tatiana and Maurage,
Claude-Alain and Sahbatou, Mourad and Liebau, Stefan and
Ding, Jinhui and Bilgic, Basar and Emre, Murat and
Erginel-Unaltuna, Nihan and Guven, Gamze and Tison,
François and Tranchant, Christine and Vidailhet, Marie and
Corvol, Jean-Christophe and Krack, Paul and Leutenegger,
Anne-Louise and Nalls, Michael A and Hernandez, Dena G and
Heutink, Peter and Gibbs, J Raphael and Hardy, John and
Wood, Nicholas W and Gasser, Thomas and Durr, Alexandra and
Deleuze, Jean-François and Tazir, Meriem and Destée, Alain
and Lohmann, Ebba and Kabashi, Edor and Singleton, Andrew
and Corti, Olga and Brice, Alexis and Study, French
Parkinson's Disease Genetics and Consortium, International
Parkinson's Disease Genomics and Lesage, Suzanne and Tison,
François and Vidailhet, Marie and Corvol, Jean-Christophe
and Agid, Yves and Anheim, Mathieu and Bonnet, Anne-Marie
and Borg, Michel and Broussolle, Emmanuel and Damier,
Philippe and Destée, Alain and Durif, Franck and Krack,
Paul and Klebe, Stephan and Martinez, Maria and Pollak,
Pierre and Rascol, Olivier and Tranchant, Christine and
Vérin, Marc and Viallet, François and Brice, Alexis and
Lesage, Suzanne and Majounie, Elisa and Tison, François and
Vidailhet, Marie and Corvol, Jean Christophe and Nalls,
Michael A and Gibbs, J Raphael and Arepalli, Sampath and
Barker, Roger A and Bettella, Francesco and Bhatia, Kailash
and de Bie, Rob M A and Biffi, Alessandro and Bloem,
Bastiaan R and Bochdanovits, Zoltan and Bonin, Michael and
Lesage, Suzanne and Tison, François and Vidailhet, Marie
and Corvol, Jean-Christophe and Agid, Yves and Anheim,
Mathieu and Bonnet, Anne-Marie and Borg, Michel and
Broussolle, Emmanuel and Damier, Philippe and Destée, Alain
and Durif, Franck and Krack, Paul and Klebe, Stephan and
Martinez, Maria and Pollak, Pierre and Rascol, Olivier and
Tranchant, Christine and Vérin, Marc and Bras, Jose M and
Brooks, Janet and Burn, David J and Charlesworth, Gavin and
Chen, Honglei and Chinnery, Patrick F and Chong, Sean and
Clarke, Carl E and Cookson, Mark R and Counsell, Carl and
Damier, Philippe and Dartigues, Jean-François and Deloukas,
Panos and Deuschl, Günther and Dexter, David T and van
Dijk, Karin D and Dillman, Allissa and Dong, Jing and Durif,
Frank and Edkins, Sarah and Escott-Price, Valentina and
Evans, Jonathan R and Foltynie, Thomas and Gao, Jianjun and
Gardner, Michelle and Goate, Alison and Gray, Emma and
Guerreiro, Rita and Harris, Clare and van Hilten, Jacobus J
and Hofman, Albert and Hollenbeck, Albert and Holmans, Peter
and Holton, Janice and Hu, Michèle and Huang, Xuemei and
Hudson, Gavin and Hunt, Sarah E and Huttenlocher, Johanna
and Illig, Thomas and Jónsson, Pálmi V and Kilarski, Laura
L and Lambert, Jean-Charles and Langford, Cordelia and Lees,
Andrew and Lichtner, Peter and Limousin, Patricia and Lopez,
Grisel and Lorenz, Delia and Lubbe, Steven and Lungu, Codrin
and Martinez, María and Mätzler, Walter and McNeill,
Alisdair and Moorby, Catriona and Moore, Matthew and
Morrison, Karen E and Mudanohwo, Ese and O'Sullivan, Sean S
and Owen, Michael J and Pearson, Justin and Perlmutter, Joel
S and Pétursson, Hjörvar and Plagnol, Vincent and Pollak,
Pierre and Post, Bart and Potter, Simon and Ravina, Bernard
and Revesz, Tamas and Riess, Olaf and Rivadeneira, Fernando
and Ryten, Mina and Saad, Mohamad and Simón-Sánchez,
Javier and Sawcer, Stephen and Schapira, Anthony and
Scheffer, Hans and Shaw, Karen and Sheerin, Una-Marie and
Shoulson, Ira and Shulman, Joshua and Sidransky, Ellen and
Spencer, Chris C A and Stefánsson, Hreinn and Stefánsson,
Kári and Stockton, Joanna D and Strange, Amy and Talbot,
Kevin and Tanner, Carlie M and Tashakkori-Ghanbaria, Avazeh
and Trabzuni, Daniah and Traynor, Bryan J and Uitterlinden,
André G and Velseboer, Daan and Walker, Robert and van de
Warrenburg, Bart and Wickremaratchi, Mirdhu and
Williams-Gray, Caroline H and Winder-Rhodes, Sophie and
Williams, Nigel and Morris, Huw R and Hardy, John and Wood,
Nicholas W and Singleton, Andrew B and Brice, Alexis},
title = {{L}oss of {VPS}13{C} {F}unction in {A}utosomal-{R}ecessive
{P}arkinsonism {C}auses {M}itochondrial {D}ysfunction and
{I}ncreases {PINK}1/{P}arkin-{D}ependent {M}itophagy.},
journal = {The American journal of human genetics},
volume = {98},
number = {3},
issn = {0002-9297},
address = {New York, NY},
publisher = {Elsevier},
reportid = {DZNE-2020-04778},
pages = {500-513},
year = {2016},
abstract = {Autosomal-recessive early-onset parkinsonism is clinically
and genetically heterogeneous. The genetic causes of
approximately $50\%$ of autosomal-recessive early-onset
forms of Parkinson disease (PD) remain to be elucidated.
Homozygozity mapping and exome sequencing in 62 isolated
individuals with early-onset parkinsonism and confirmed
consanguinity followed by data mining in the exomes of 1,348
PD-affected individuals identified, in three isolated
subjects, homozygous or compound heterozygous truncating
mutations in vacuolar protein sorting 13C (VPS13C). VPS13C
mutations are associated with a distinct form of early-onset
parkinsonism characterized by rapid and severe disease
progression and early cognitive decline; the pathological
features were striking and reminiscent of diffuse Lewy body
disease. In cell models, VPS13C partly localized to the
outer membrane of mitochondria. Silencing of VPS13C was
associated with lower mitochondrial membrane potential,
mitochondrial fragmentation, increased respiration rates,
exacerbated PINK1/Parkin-dependent mitophagy, and
transcriptional upregulation of PARK2 in response to
mitochondrial damage. This work suggests that loss of
function of VPS13C is a cause of autosomal-recessive
early-onset parkinsonism with a distinctive phenotype of
rapid and severe progression.},
keywords = {Adult / Aged / Animals / COS Cells / Case-Control Studies /
Consanguinity / Female / Gene Silencing / Genetic
Heterogeneity / HEK293 Cells / Heterozygote / Homozygote /
Humans / Male / Middle Aged / Mitophagy: genetics /
Parkinsonian Disorders: diagnosis / Parkinsonian Disorders:
genetics / Pedigree / Phenotype / Protein Kinases: genetics
/ Protein Kinases: metabolism / Proteins: genetics /
Proteins: metabolism / Reproducibility of Results / Turkey /
Ubiquitin-Protein Ligases: genetics / Ubiquitin-Protein
Ligases: metabolism / Proteins (NLM Chemicals) / VPS13C
protein, human (NLM Chemicals) / Ubiquitin-Protein Ligases
(NLM Chemicals) / parkin protein (NLM Chemicals) / Protein
Kinases (NLM Chemicals) / PTEN-induced putative kinase (NLM
Chemicals)},
cin = {AG Heutink / AG Gasser},
ddc = {570},
cid = {I:(DE-2719)1210002 / I:(DE-2719)1210000},
pnm = {345 - Population Studies and Genetics (POF3-345)},
pid = {G:(DE-HGF)POF3-345},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:26942284},
pmc = {pmc:PMC4800038},
doi = {10.1016/j.ajhg.2016.01.014},
url = {https://pub.dzne.de/record/138456},
}