Cathepsin B p.Gly284Val Variant in Parkinson's Disease Pathogenesis
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F22%3A00076290" target="_blank" >RIV/00159816:_____/22:00076290 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14740/22:00127440
Result on the web
<a href="https://www.mdpi.com/1422-0067/23/13/7086" target="_blank" >https://www.mdpi.com/1422-0067/23/13/7086</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/ijms23137086" target="_blank" >10.3390/ijms23137086</a>
Alternative languages
Result language
angličtina
Original language name
Cathepsin B p.Gly284Val Variant in Parkinson's Disease Pathogenesis
Original language description
Parkinson's disease (PD) is generally considered a sporadic disorder, but a strong genetic background is often found. The aim of this study was to identify the underlying genetic cause of PD in two affected siblings and to subsequently assess the role of mutations in Cathepsin B (CTSB) in susceptibility to PD. A typical PD family was identified and whole-exome sequencing was performed in two affected siblings. Variants of interest were validated using Sanger sequencing. CTSB p.Gly284Val was genotyped in 2077 PD patients and 615 unrelated healthy controls from the Czech Republic, Ireland, Poland, Ukraine, and the USA. The gene burden analysis was conducted for the CTSB gene in an additional 769 PD probands from Mayo Clinic Florida familial PD cohort. CTSB expression and activity in patient-derived fibroblasts and controls were evaluated by qRT-PCR, western blot, immunocytochemistry, and enzymatic assay. The CTSB p.Gly284Val candidate variant was only identified in affected family members. Functional analysis of CTSB patient-derived fibroblasts under basal conditions did not reveal overt changes in endogenous expression, subcellular localization, or enzymatic activity in the heterozygous carrier of the CTSB variant. The identification of the CTSB p.Gly284Val may support the hypothesis that the CTSB locus harbors variants with differing penetrance that can determine the disease risk.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30100 - Basic medicine
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
International Journal of Molecular Sciences
ISSN
1422-0067
e-ISSN
1422-0067
Volume of the periodical
23
Issue of the periodical within the volume
13
Country of publishing house
CH - SWITZERLAND
Number of pages
12
Pages from-to
nestrankovano
UT code for WoS article
000824355700001
EID of the result in the Scopus database
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