Analysis of mutations associated with Parkinson’s disease in patients of the Krasnoyarsk region

2021 ◽  
Vol 26 (4) ◽  
pp. 15-22
Author(s):  
T. N. Subbotina ◽  
V. G. Abramov ◽  
A. A. Razumova ◽  
G. Y. Kochmaryova ◽  
A. A. Karnyushka ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Point Mutations ◽  
Compound Heterozygous ◽  
Similar Frequency ◽  
Krasnoyarsk Region ◽  
Increased Risk ◽  
Lrrk2 Gene ◽  
Synonymous Variant ◽  
Gba Gene

Background. Parkinson’s disease (PD) is one of the common neurodegenerative diseases. Several genes are known (SNCA, PARK2, PINK1, PARK7 (DJ-1) and LRRK2), mutations in which have a pathological significance in the development of monogenic PD; association with PD of other genes (for example, UCHL1, ATP13A2) requires further study. It is also known, that GBA gene is associated with an increased risk of PD developing.Aim. Analysis of mutations and polymorphisms in the PARK2, PINK1, SNCA, ATP13A2, PARK7, LRRK2, UCHL, GCH1 and GBA genes in patients with PD from Krasnoyarsk region.Material and methods. The 60 patients with sporadic and familial forms of PD were included in the study. The SALSA MLPA Holland P051 and P052 kits («MRC Amsterdam», The Netherlands) were used to detect deletions and duplications in the PARK2, PINK1, SNCA, ATP13A2, PARK7, LRRK2, UCHL, GCH1 genes, as well as point mutations A30P in the SNCA gene and G2019S in the LRRK2 gene. Analysis of the GBA gene was carried out by Senger sequencing.Results. None of the 60 patients had mutations that were searched with the SALSA MLPA Holland P051 and P052 kits. 6 different mutations in the GBA gene were found in 9 out of 60 patients with PD. L444P («severe» PD — associated mutation) — in two patients, D409H («severe» PD — associated mutation) — in one patient, T369M (polymorphism, possibly associated with PD) — in two patients, E326K (polymorphism, possibly associated with PD) — in one patient, V460V (synonymous variant, which is part of the composition of the complex RecNcil mutation (p.L444P; p.A456P; p.V460V) associated with PD) — in two patients and variant C.*92g>A (3’ — UTR polymorphism, possibly associated with PD) — in one patient. Two patients had compound heterozygous carriers of two variants.Conclusion. This paper presents the genetic analysis results of the PD associated genes among patients from the Krasnoyarsk region. No mutations were detected in the PARK2, PINK1, SNCA, ATP13A2, PARK7, LRRK2, UCHL and GCH1 genes. Genetic variants analysis of the GBA gene showed similar frequency in the patients from the Krasnoyarsk region as in European populations.

scholarly journals Study of The Collagen Type VI Alpha 3 (COL6A3) Gene in Parkinson’s Disease

2021 ◽  
Author(s):  
Chong-Yao Jin ◽  
Ran Zheng ◽  
Zhi-Hao Lin ◽  
Nai-Jia Xue ◽  
Ying Chen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Collagen Type ◽  
Gene Mutations ◽  
Compound Heterozygous ◽  
Genetic Characteristics ◽  
Increased Risk ◽  
Collagen Type Vi ◽  
Chinese Cohort ◽  
Aggregate Burden

Abstract Background To date, the genetic contribution to Parkinson’s disease (PD) remains unclear. Mutations in the collagen type VI alpha 3 (COL6A3) gene were recently identified as a cause of isolated dystonia. Since PD and dystonia are closely related disorders with shared clinical and genetic characteristics, we explored the association between COL6A3 and PD in a Chinese cohort. Methods We performed genetic screening of COL6A3 in a Chinese cohort of 173 patients with sporadic PD and 200 healthy controls. We identified variants that are likely to have pathogenic effects based on: 1) a minor allele frequency of < 0.01; and 2) the variant being recognized as deleterious by at least 15 different in silico predicting tools. Finally, we tested the aggregate burden of COL6A3 on PD via SKAT-O analysis. Results First, we found compound heterozygous COL6A3 gene mutations in one early-onset PD patients. Then, we explored whether COL6A3 variants contributed to increased risk of developing PD in a Chinese population. We detected 21 rare non-synonymous variants. Pathogenicity predictions identified seven novel non-synonymous variants as likely to be pathogenic. SKAT-O analysis further revealed that an aggregate burden of variants in COL6A3 contributes to PD (p = 0.03). Conclusion An increased aggregate burden of the COL6A3 gene was detected in patients with PD.

scholarly journals Contribution of rare homozygous and compound heterozygous VPS13C missense mutations to dementia with Lewy bodies and Parkinson’s disease

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Stefanie Smolders ◽  
◽  
Stéphanie Philtjens ◽  
David Crosiers ◽  
Anne Sieben ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Onset ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Lewy Body Disease ◽  
Compound Heterozygous ◽  
Missense Mutations ◽  
Increased Risk ◽  
Vacuolar Protein

AbstractDementia with Lewy bodies (DLB) and Parkinson’s disease (PD) are clinically, pathologically and etiologically disorders embedded in the Lewy body disease (LBD) continuum, characterized by neuronal α-synuclein pathology. Rare homozygous and compound heterozygous premature termination codon (PTC) mutations in the Vacuolar Protein Sorting 13 homolog C gene (VPS13C) are associated with early-onset recessive PD. We observed in two siblings with early-onset age (< 45) and autopsy confirmed DLB, compound heterozygous missense mutations in VPS13C, p.Trp395Cys and p.Ala444Pro, inherited from their healthy parents in a recessive manner. In lymphoblast cells of the index patient, the missense mutations reduced VPS13C expression by 90% (p = 0.0002). Subsequent, we performed targeted resequencing of VPS13C in 844 LBD patients and 664 control persons. Using the optimized sequence kernel association test, we obtained a significant association (p = 0.0233) of rare VPS13C genetic variants (minor allele frequency ≤ 1%) with LBD. Among the LBD patients, we identified one patient with homozygous missense mutations and three with compound heterozygous missense mutations in trans position, indicative for recessive inheritance. In four patients with compound heterozygous mutations, we were unable to determine trans position. The frequency of LBD patient carriers of proven recessive compound heterozygous missense mutations is 0.59% (5/844). In autopsy brain tissue of two unrelated LBD patients, the recessive compound heterozygous missense mutations reduced VPS13C expression. Overexpressing of wild type or mutant VPS13C in HeLa or SH-SY5Y cells, demonstrated that the mutations p.Trp395Cys or p.Ala444Pro, abolish the endosomal/lysosomal localization of VPS13C. Overall, our data indicate that rare missense mutations in VPS13C are associated with LBD and recessive compound heterozygous missense mutations might have variable effects on the expression and functioning of VPS13C. We conclude that comparable to the recessive inherited PTC mutations in VPS13C, combinations of rare recessive compound heterozygous missense mutations reduce VPS13C expression and contribute to increased risk of LBD.

scholarly journals Study of the collagen type VI alpha 3 (COL6A3) gene in Parkinson’s disease

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chong-Yao Jin ◽  
Ran Zheng ◽  
Zhi-Hao Lin ◽  
Nai-Jia Xue ◽  
Ying Chen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Collagen Type ◽  
Gene Mutations ◽  
Compound Heterozygous ◽  
Genetic Characteristics ◽  
Increased Risk ◽  
Collagen Type Vi ◽  
Chinese Cohort ◽  
Aggregate Burden

Abstract Background To date, the genetic contribution to Parkinson’s disease (PD) remains unclear. Mutations in the collagen type VI alpha 3 (COL6A3) gene were recently identified as a cause of isolated dystonia. Since PD and dystonia are closely related disorders with shared clinical and genetic characteristics, we explored the association between COL6A3 and PD in a Chinese cohort. Methods We performed genetic screening of COL6A3 in a Chinese cohort of 173 patients with sporadic PD and 200 healthy controls. We identified variants that are likely to have pathogenic effects based on: 1) a minor allele frequency of < 0.01; and 2) the variant being recognized as deleterious by at least 15 different in silico predicting tools. Finally, we tested the aggregate burden of COL6A3 on PD via SKAT-O analysis. Results First, we found compound heterozygous COL6A3 gene mutations in one early-onset PD patients. Then, we explored whether COL6A3 variants contributed to increased risk of developing PD in a Chinese population. We detected 21 rare non-synonymous variants. Pathogenicity predictions identified 7 novel non-synonymous variants as likely to be pathogenic. SKAT-O analysis further revealed that an aggregate burden of variants in COL6A3 contributes to PD (p = 0.038). Conclusion An increased aggregate burden of the COL6A3 gene was detected in patients with PD.

scholarly journals A-079 Hand Preference in Men and Women with Parkinson’s Disease: A Preliminary Investigation

2020 ◽  
Vol 35 (6) ◽  
pp. 871-871
Author(s):  
Ryan J ◽  
Kreiner D ◽  
Gontkovsky S ◽  
Paolo A
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurological Disorders ◽  
Rating Scale ◽  
Preliminary Investigation ◽  
Hand Preference ◽  
Dominant Hand ◽  
Healthy Individuals ◽  
Left Handed ◽  
Increased Risk

Abstract Objective Research has identified common genetic influences on handedness and neurological/mental health phenotypes. It also has been shown there may be increased risk for development of neurological disorders/diseases among individuals naturally left-handed or demonstrating non-right-hand preference. This investigation examined prevalence of right-handed versus non-right-handed individuals with Parkinson’s disease (PD) compared to controls. Method Participants were 264 patients with PD (mean age = 69.83 years) and 256 control volunteers (mean age = 71.42 years). Mean Dementia Rating Scale composites for the groups were 123.68 and 136.00, respectively. Participants self-identified their dominant hand for writing and usage was confirmed during the session. Results Proportions of non-right- and right-handed controls (7.0% and 93.0%) versus individuals with PD (6.8% and 93.2%) did not differ. Changes in proportions of non-right- and right-handedness across age ranges were not significant for controls or patients. There was a trend for a larger proportion of women (55.9%) versus men among controls (44.1%), □ 2 (1) = 3.29, p &lt; .10; whereas, the proportion of men (64.4%) with PD was larger than that of women. (35.6%), □ 2 (1) = 21.31, p &lt; .001. For controls and patients, non-right and right handedness gender proportions were similar. Conclusions This study is the first to assess handedness prevalence rates in PD. Results suggest prevalence of non-right handedness is similar in PD and healthy individuals and does not appear to differ markedly by gender or with advancing age. The occurrence of a trend for a larger proportion of women than men among controls is consistent with census-based statistics.

Migraine is related to an increased risk of Parkinson’s disease: A population-based, propensity score-matched, longitudinal follow-up study

Cephalalgia ◽  
2016 ◽  
Vol 36 (14) ◽  
pp. 1316-1323 ◽  
Author(s):  
Hsin-I Wang ◽  
Yu-Chun Ho ◽  
Ya-Ping Huang ◽  
Shin-Liang Pan
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Survival Rate ◽  
Propensity Score ◽  
Population Based ◽  
Free Survival ◽  
Follow Up Study ◽  
Increased Risk ◽  
Migraine Group

Background The association between migraine and Parkinson’s disease (PD) remains controversial. The purpose of the present population-based, propensity score-matched follow-up study was to investigate whether migraineurs are at a higher risk of developing PD. Methods A total of 41,019 subjects aged between 40 and 90 years with at least two ambulatory visits with a diagnosis of migraine in 2001 were enrolled in the migraine group. A logistic regression model that included age, sex, pre-existing comorbidities and socioeconomic status as covariates was used to compute the propensity score. The non-migraine group consisted of 41,019 propensity score-matched, randomly sampled subjects without migraine. The PD-free survival rate were estimated using the Kaplan–Meier method. Stratified Cox proportional hazard regression was used to estimate the effect of migraine on the risk of developing PD. Results During follow-up, 148 subjects in the migraine group and 101 in the non-migraine group developed PD. Compared to the non-migraine group, the hazard ratio of PD for the migraine group was 1.64 (95% confidence interval: 1.25–2.14, p = 0.0004). The PD-free survival rate for the migraine group was significantly lower than that for the non-migraine group ( p = 0.0041). Conclusions This study showed an increased risk of developing PD in patients with migraine.

scholarly journals Dietary intake of folate, vitamin B6, vitamin B12 and riboflavin and risk of Parkinson's disease: a case–control study in Japan

2010 ◽  
Vol 104 (5) ◽  
pp. 757-764 ◽  
Author(s):  
Kentaro Murakami ◽  
Yoshihiro Miyake ◽  
Satoshi Sasaki ◽  
Keiko Tanaka ◽  
Wakaba Fukushima ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dietary Intake ◽  
Case Control Study ◽  
Case Control ◽  
B Vitamins ◽  
Vitamin B ◽  
Increased Risk ◽  
The Uk ◽  
Control Study

Increased homocysteine levels might accelerate dopaminergic cell death in Parkinson's disease (PD) through neurotoxic effects; thus, increasing intake of B vitamins involved in the regulation of homocysteine metabolism might decrease the risk of PD through decreasing plasma homocysteine. However, epidemiological evidence for the association of dietary B vitamins with PD is sparse, particularly in non-Western populations. We conducted a hospital-based case–control study in Japan to examine associations between dietary intake of folate, vitamin B6, vitamin B12 and riboflavin and the risk of PD. Patients with PD diagnosed using the UK PD Society Brain Bank criteria (n 249) and controls without neurodegenerative diseases (n 368) were recruited. Dietary intake during the preceding month was assessed at the time of study recruitment using a validated, self-administered, semi-quantitative, comprehensive diet history questionnaire. After adjustment for potential dietary and non-dietary confounding factors, intake of folate, vitamin B12 and riboflavin was not associated with the risk of PD (P for trend = 0·87, 0·70 and 0·11, respectively). However, low intake of vitamin B6 was associated with an increased risk of PD, independent of potential dietary and non-dietary confounders. Multivariate OR (95 % CI) for PD in the first, second, third and fourth quartiles of vitamin B6 were 1 (reference), 0·56 (0·33, 0·94), 0·69 (0·38, 1·25) and 0·48 (0·23, 0·99), respectively (P for trend = 0·10). In conclusion, in the present case–control study in Japan, low intake of vitamin B6, but not of folate, vitamin B12 or riboflavin, was independently associated with an increased risk of PD.

scholarly journals The “Gender Factor” in Wearing-Off among Patients with Parkinson’s Disease: A Post Hoc Analysis of DEEP Study

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Delia Colombo ◽  
Giovanni Abbruzzese ◽  
Angelo Antonini ◽  
Paolo Barone ◽  
Gilberto Bellia ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cross Sectional Study ◽  
Motor Symptom ◽  
Cross Sectional ◽  
Post Hoc Analysis ◽  
Increased Risk ◽  
Wearing Off ◽  
Gender Factor ◽  
Post Hoc

Background. The early detection of wearing-off in Parkinson disease (DEEP) observational study demonstrated that women with Parkinson’s disease (PD) carry an increased risk (80.1%) for wearing-off (WO). This post hoc analysis of DEEP study evaluates gender differences on WO and associated phenomena.Methods. Patients on dopaminergic treatment for ≥1 year were included in this multicenter observational cross-sectional study. In a single visit, WO was diagnosed based on neurologist assessment as well as the use of the 19-item wearing-off questionnaire (WOQ-19); WO was defined for scores ≥2. Post hoc analyses were conducted to investigate gender difference for demographic and clinical features with respect to WO.Results. Of 617 patients enrolled, 236 were women and 381 were men. Prevalence of WO was higher among women, according to both neurologists’ judgment (61.9% versus 53.8%,P=0.045) and the WOQ-19 analysis (72.5% versus 64.0%,P=0.034). In patients with WO (WOQ-19), women experienced ≥1 motor symptom in 72.5% versus 64.0% in men and ≥1 nonmotor symptom in 44.5% versus 36.7%, in men.Conclusions. Our results suggest WO as more common among women, for both motor and nonmotor symptoms. Prospective studies are warranted to investigate this potential gender-effect.

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