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Loss of VPS13C Function in Autosomal-Recessive Parkinsonism Causes Mitochondrial Dysfunction and Increases PINK1/Parkin-Dependent Mitophagy
Lesage S, Drouet V, Majounie E, Deramecourt V, Jacoupy M, Nicolas A, Cormier-Dequaire F, Hassoun SM et al.. American journal of human genetics, 2016-03-01
Topic: Brain proteins, microglia and lab models
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.
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APA 7th
Lesage, S., Drouet, V., Majounie, E., Deramecourt, V., Jacoupy, M., Nicolas, A., et al. (2016). Loss of VPS13C Function in Autosomal-Recessive Parkinsonism Causes Mitochondrial Dysfunction and Increases PINK1/Parkin-Dependent Mitophagy. American journal of human genetics. https://doi.org/10.1016/j.ajhg.2016.01.014
Vancouver
Lesage S, Drouet V, Majounie E, Deramecourt V, Jacoupy M, Nicolas A, et al. Loss of VPS13C Function in Autosomal-Recessive Parkinsonism Causes Mitochondrial Dysfunction and Increases PINK1/Parkin-Dependent Mitophagy. American journal of human genetics. 2016. doi:10.1016/j.ajhg.2016.01.014. PMID: 26942284.
BibTeX
@article{lesage2016-26942284,
author = {Lesage, S. and Drouet, V. and Majounie, E. and Deramecourt, V. and Jacoupy, M. and Nicolas, A. and Cormier-Dequaire, F. and Hassoun, S. M. and others},
title = {{Loss of VPS13C Function in Autosomal-Recessive Parkinsonism Causes Mitochondrial Dysfunction and Increases PINK1/Parkin-Dependent Mitophagy}},
journal = {American journal of human genetics},
year = {2016},
doi = {10.1016/j.ajhg.2016.01.014},
pmid = {26942284},
url = {https://doi.org/10.1016/j.ajhg.2016.01.014}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- 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.
- 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.
Why it matters
Mutations in VPS13C were found to cause an early-onset form of parkinsonism with rapid progression and early cognitive decline, and silencing VPS13C in cell models caused mitochondrial dysfunction and increased mitophagy. This is genetic and cell-model research into a parkinsonism-related condition, not a treatment or prevention for Alzheimer's disease.
Study details
- Evidence strengthLow
How this study scored 52/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 50 of the 96 points we could judge it on, which is 52 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (American journal of human genetics) |
| Journal's citation record | 3 / 4 | The American Journal of Human Genetics: journal h-index 385 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2016 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 434 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 36.2 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 5 / 6 | Cited 26.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 3 / 4 | Cited 115 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 3 / 3 | National Institutes of Health: institution h-index 2,723 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 34 institution(s) in 6 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 26942284) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 50 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 50 of the 96 points we could judge it on is 52 out of 100. |
| Total | 52 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.ajhg.2016.01.014
- PubMed: 26942284
- Original source →
- Free full text: The American Journal of Human Genetics →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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