Lesage 2016 Am J Hum Genet

[[Has title::Lesage S, Drouet V, Majounie E, Deramecourt V, Jacoupy M, Nicolas A, Cormier-Dequaire F, Hassoun SM, Pujol C, Ciura S, Erpapazoglou Z, Usenko T, Maurage CA, Sahbatou M, Liebau S, Ding J, Bilgic B, Emre M, Erginel-Unaltuna N, Guven G, Tison F, Tranchant C, Vidailhet M, Corvol JC, Krack P, Leutenegger AL, Nalls MA, Hernandez DG, Heutink P, Gibbs JR, Hardy J, Wood NW, Gasser T, Durr A, Deleuze JF, Tazir M, Destée A, Lohmann E, Kabashi E, Singleton A, Corti O, Brice A (2016) Loss of VPS13C function in autosomal-recessive parkinsonism causes mitochondrial dysfunction and increases PINK1/Parkin-Dependent Mitophagy. Am J Hum Genet 98:500-13.]]

» [[Has info::PMID: 26942284]]

Was written by::Lesage S, Was written by::Drouet V, Was written by::Majounie E, Was written by::Deramecourt V, Was written by::Jacoupy M, Was written by::Nicolas A, Was written by::Cormier-Dequaire F, Was written by::Hassoun SM, Was written by::Pujol C, Was written by::Ciura S, Was written by::Erpapazoglou Z, Was written by::Usenko T, Was written by::Maurage CA, Was written by::Sahbatou M, Was written by::Liebau S, Was written by::Ding J, Was written by::Bilgic B, Was written by::Emre M, Was written by::Erginel-Unaltuna N, Was written by::Guven G, Was written by::Tison F, Was written by::Tranchant C, Was written by::Vidailhet M, Was written by::Corvol JC, Was written by::Krack P, Was written by::Leutenegger AL, Was written by::Nalls MA, Was written by::Hernandez DG, Was written by::Heutink P, Was written by::Gibbs JR, Was written by::Hardy J, Was written by::Wood NW, Was written by::Gasser T, Was written by::Durr A, Was written by::Deleuze JF, Was written by::Tazir M, Was written by::Destée A, Was written by::Lohmann E, Was written by::Kabashi E, Was written by::Singleton A, Was written by::Corti O, Was written by::Brice A (Was published in year::2016) Was published in journal::Am J Hum Genet

Abstract: [[has 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.

Labels: MiParea: MiP area::Respiration, MiP area::nDNA;cell genetics, MiP area::Genetic knockout;overexpression Pathology: Diseases::Parkinson's

Organism: Organism::Other mammals Tissue;cell: tissue and cell::Kidney, tissue and cell::Other cell lines Preparation: Preparation::Intact cells

Coupling state: Coupling states::LEAK, Coupling states::ROUTINE, Coupling states::ETS Pathway: Pathways::ROX HRR: Instrument and method::Oxygraph-2k

additional label::2016-05