Familial atypical parkinsonism with rare variant in VPS35 and FBXO7 genes

Bartoníková, Tereza; Menšíková, Kateřina; Mikulicova, Lenka; Vodička, Radek; Vrtěl, Radek; Godava, Marek; Vaštík, Miroslav; Kaiserová, Michaela; Otruba, Pavel; Dolinová, Iva; Nevrlý, Martin; Kaňovský, Petr

doi:10.1097/md.0000000000005398

Cited by 10 publications

(5 citation statements)

References 23 publications

(14 reference statements)

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“…For the planned functional analyses, we have so far collected only one brain specimen from the research pedigreee. [ 31 ] Therefore, our future study will also utilize proper cell lines with combinations of targeted mutagenesis to assess the effects of particular rare variants.…”

Section: Discussionmentioning

confidence: 99%

New endemic familial parkinsonism in south Moravia, Czech Republic and its genetical background

Bartoníková¹,

Menšíková²,

Kolaříková

et al. 2018

Medicine

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An increased prevalence of familial neurodegenerative parkinsonism or cognitive deterioration was recently found in a small region of southeastern Moravia.The aim of the study was to assess the genetic background of this familial disease.Variants in the ADH1C, EIF4G1, FBXO7, GBA + GBAP1, GIGYF2, HTRA2, LRRK2, MAPT, PRKN, DJ-1, PINK1, PLA2G6, SNCA, UCHL1, VPS35 genes were examined in 12 clinically positive probands of the pedigree in which familial atypical neurodegenerative parkinsonism was identified in previous epidemiological studies. Libraries were sequenced by massive parallel sequencing (MPS) on the Personal Genome Machine (PGM; Ion Torrent). Data were analyzed using Torrent Suite and IonReporter software. All variants were then verified and confirmed by Sanger sequencing.We identified 31 rare heterozygous variants: 11 missense variants, 3 synonymous variants, 8 variants in the UTR region, and 9 intronic variants. Six variants (rs1801334, rs33995883, rs35507033, rs781737269, rs779760087, and rs63750072) were evaluated as pathogenic by at least one in-silico predictor.No single “founder” pathogenic variant associated with parkinsonism has been found in any of the probands from researched pedigree. It may rather be assumed that the familial occurrence of this disease is caused by the combined influence of several “small-effect” genetic variants that accumulate in the population with long-lasting inbreeding behavior.

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Section: Discussionmentioning

confidence: 99%

New endemic familial parkinsonism in south Moravia, Czech Republic and its genetical background

Bartoníková¹,

Menšíková²,

Kolaříková

et al. 2018

Medicine

Self Cite

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“…The genetic aspects of the disease are linked to mutations in several genes related to a multitude of cellular mechanisms, such as protein aggregation, protein and membrane trafficking, lysosomal autophagy, immune response, synaptic function, endocytosis, inflammation, and metabolic pathways (Redenšek et al, 2017 ). The genes SNCA (PARK1), UCHL1 (PARK5), LRRK2 (PARK8), GIGYF2 (PARK11), OMI/HTRA2 (PARK13), VPS35 (PARK17), and EIF4G1 (PARK18) result in autosomal dominant PD, and PRKN (PARK2), DJ-1 (PARK7), ATP13A2 (PARK9), PLA2G6 (PARK14), FBX07 (PARK15), DNJC6 (PARK19), and SYNJ1 (PARK20) causes autosomal recessive PD (Lautier et al, 2008 ; Di Fonzo et al, 2009 ; Klein and Westenberger, 2012 ; Deng et al, 2015 ; Bartonikova et al, 2016 ; Miki et al, 2017 ; Scott et al, 2017 ). The gene contribution from other loci (PARK 3, 10, 12, and 16) is under investigation (Dawson and Dawson, 2010 ).…”

Section: General Aspects Of Parkinson's Diseasementioning

confidence: 99%

Targeting Adenosine Signaling in Parkinson's Disease: From Pharmacological to Non-pharmacological Approaches

2017

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Parkinson's disease (PD) is one of the most prevalent neurodegenerative disease displaying negative impacts on both the health and social ability of patients and considerable economical costs. The classical anti-parkinsonian drugs based in dopaminergic replacement are the standard treatment, but several motor side effects emerge during long-term use. This mini-review presents the rationale to several efforts from pre-clinical and clinical studies using adenosine receptor antagonists as a non-dopaminergic therapy. As several studies have indicated that the monotherapy with adenosine receptor antagonists reaches limited efficacy, the usage as a co-adjuvant appeared to be a promising strategy. The formulation of multi-targeted drugs, using adenosine receptor antagonists and other neurotransmitter systems than the dopaminergic one as targets, have been receiving attention since Parkinson's disease presents a complex biological impact. While pharmacological approaches to cure or ameliorate the conditions of PD are the leading strategy in this area, emerging positive aspects have arisen from non-pharmacological approaches and adenosine function inhibition appears to improve both strategies.

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“…They also found a positive applauding sign, postural instability and cognitive disorder (MMSE 23/30). During the course of disease, in addition, supranuclear gaze palsy, apraxia of lid opening, dysarthria, dysphagia severe dementia (MMSE 16/30) and inability to walk occurred [19].…”

Section: Clinical Presentationmentioning

confidence: 99%

VPS35-Linked Parkinson’s Disease Resembles the Idiopathic Disease: A Review of Clinical Trials

Brim¹,

Gerhard²,

Zimprich³

et al. 2017

J Alzheimers Dis Parkinsonism

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Familial atypical parkinsonism with rare variant in VPS35 and FBXO7 genes

Abstract: Supplemental Digital Content is available in the text

Cited by 10 publications

References 23 publications

New endemic familial parkinsonism in south Moravia, Czech Republic and its genetical background

New endemic familial parkinsonism in south Moravia, Czech Republic and its genetical background

Targeting Adenosine Signaling in Parkinson's Disease: From Pharmacological to Non-pharmacological Approaches

VPS35-Linked Parkinson’s Disease Resembles the Idiopathic Disease: A Review of Clinical Trials

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