ArticleNPJ genomic medicine2021
Putative second hit rare genetic variants in families with seemingly GBA-associated Parkinson's disease.
Article in NPJ genomic medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 19 citations in OpenAlex.
- DNAJB6: A guardian against neurodegeneration.Neural regeneration research · 2026Article
- Prosaposin in CNS health and disease, metabolic stress and exercise adaptation.Journal of molecular medicine (Berlin, Germany) · 2026Review
- The Role of α-Synuclein-DNAJB6b Coaggregation in Amyloid Suppression.ACS chemical neuroscience · 2025Article
- Article
- Decoding chaperone complexes: Insights from NMR spectroscopy.Biophysics reviews · 2024Review
- Review
- GBA-associated Parkinson's disease in Hungary: clinical features and genetic insights.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Article
- Prosaposin maintains lipid homeostasis in dopamine neurons and counteracts experimental parkinsonism in rodents.Nature communications · 2023Article
- Clinical and genetic analysis of Vietnamese patients diagnosed with early-onset Parkinson's disease.Brain and behavior · 2023Article
- Who is at Risk of Parkinson Disease? Refining the Preclinical Phase of GBA1 and LRRK2 Variant Carriers: a Clinical, Biochemical, and Imaging Approach.Current neurology and neuroscience reports · 2023Review
- Anderson-Fabry Disease: A New Piece of the Lysosomal Puzzle in Parkinson Disease?Biomedicines · 2022Review
- Genotype by environment interactions for chronic wasting disease in farmed US white-tailed deer.G3 (Bethesda, Md.) · 2022Article
- Large Chaperone Complexes Through the Lens of Nuclear Magnetic Resonance Spectroscopy.Annual review of biophysics · 2022Review
- Microsecond Backbone Motions Modulate the Oligomerization of the DNAJB6 Chaperone.Angewandte Chemie (International ed. in English) · 2022Article
- Microsecond Backbone Motions Modulate the Oligomerization of the DNAJB6 Chaperone.Angewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2022Article
- PRINCESS: comprehensive detection of haplotype resolved SNVs, SVs, and methylation.Genome biology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 11 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rare variants in the beta-glucocerebrosidase gene (GBA1) are common genetic risk factors for alpha synucleinopathy, which often manifests clinically as GBA-associated Parkinson's disease (GBA-PD). Clinically, GBA-PD closely mimics idiopathic PD, but it may present at a younger age and often aggregates in families. Most carriers of GBA variants are, however, asymptomatic. Moreover, symptomatic PD patients without GBA variant have been reported in families with seemingly GBA-PD. These observations obscure the link between GBA variants and PD pathogenesis and point towards a role for unidentified additional genetic and/or environmental risk factors or second hits in GBA-PD. In this study, we explored whether rare genetic variants may be additional risk factors for PD in two families segregating the PD-associated GBA1 variants c.115+1G>A (ClinVar ID: 93445) and p.L444P (ClinVar ID: 4288). Our analysis identified rare genetic variants of the HSP70 co-chaperone DnaJ homolog subfamily B member 6 (DNAJB6) and lysosomal protein prosaposin (PSAP) as additional factors possibly influencing PD risk in the two families. In comparison to the wild-type proteins, variant DNAJB6 and PSAP proteins show altered functions in the context of cellular alpha-synuclein homeostasis when expressed in reporter cells. Furthermore, the segregation pattern of the rare variants in the genes encoding DNAJB6 and PSAP indicated a possible association with PD in the respective families. The occurrence of second hits or additional PD cosegregating rare variants has important implications for genetic counseling in PD families with GBA1 variant carriers and for the selection of PD patients for GBA targeted treatments.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.