LRRK2, GBA and SMPD1 Founder Mutations and Parkinson's Disease in Ashkenazi Jews

2016 ◽  
Vol 42 (1-2) ◽  
pp. 1-6 ◽  
Author(s):  
Efrat Dagan ◽  
Ilana Schlesinger ◽  
Alina Kurolap ◽  
Mareemar Ayoub ◽  
Maria Nassar ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Characteristics ◽  
Statistical Significance ◽  
Clinical Manifestations ◽  
Age At Diagnosis ◽  
Carrier Status ◽  
Ashkenazi Jews ◽  
Founder Mutations ◽  
Mutation Carriers

Background/Aim: Parkinson's disease (PD) is associated with mutations in LRRK2, GBA, and SMPD1 genes. We describe the clinical characteristics of PD patients related to their carrier status of the Ashkenazi founder mutations in the aforementioned genes. Methods: Ashkenazi PD patients (n = 270) were recruited following informed consent, and tested for the founder Ashkenazi mutations in the above genes. Clinical characteristics were compared between carriers and noncarriers. Homozygotes for mutations in GBA or LRRK2, and those who carried mutations in two causative genes were excluded from the analysis. Results: Five (1.85%), 54 (20%), and 22 (8.1%) PD patients carried mutations in SMPD1, GBA or LRRK2, respectively. By post hoc Bonferroni analysis, GBA carriers were singled at a significantly earlier age at diagnosis compared to noncarriers (58.06 ± 10.84 and 62.65 ± 10.86 years, respectively; p = 0.036), and due to bilateral manifestation at diagnosis compared to all other PD groups (n = 8, 15.7% compared to n = 2, 1.1%, respectively; p < 0.001). Other clinical manifestations were comparable between groups. Conclusion: Although only GBA mutation carriers, compared to noncarriers, reached statistical significance regarding age at diagnosis, it appears that LRRK2 and SMPD1 mutation carriers may reach significance with larger group numbers.

scholarly journals Frequency of Heterozygous Parkin (PRKN) Variants and Penetrance of Parkinson's Disease Risk Markers in the Population-Based CHRIS Cohort

2021 ◽  
Vol 12 ◽  
Author(s):  
Maria Paulina Castelo Rueda ◽  
Athina Raftopoulou ◽  
Martin Gögele ◽  
Max Borsche ◽  
David Emmert ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Symptoms ◽  
Large Population ◽  
Population Sample ◽  
Genotype Imputation ◽  
Carrier Status ◽  
Risk Markers ◽  
Mutation Carriers ◽  
Increased Risk

Mutations in the Parkin (PRKN) gene are the most frequent cause of autosomal recessive early-onset Parkinson's disease (PD). Heterozygous PRKN mutation carriers might also be at increased risk for developing clinical symptoms of PD. Given the high frequency of heterozygous mutations in the general population, it is essential to have better estimates of the penetrance of these variants, and to investigate, which clinical and biochemical markers are present in carriers and thus potentially useful for identifying those individuals at greater risk of developing clinical symptoms later in life. In the present study, we ascertained the frequency of heterozygous PRKN mutation carriers in a large population sample of the Cooperative Health Research in South Tyrol (CHRIS) study, and screened for reported PD risk markers. 164 confirmed heterozygous PRKN mutation carriers were compared with 2,582 controls. A higher number of heterozygous mutation carriers reported a detectable increase in an akinesia-related phenotype, and a higher percentage of carriers had manifested diabetes. We also observed lower resting heart rate in the PRKN mutation carriers. Extending our risk analyses to a larger number of potential carriers and non-carriers using genotype imputation (n = 299 carriers and n = 7,127 non-carriers), from previously published biomarkers we also observed a higher neutrophil-to-lymphocyte ratio (NLR) and lower serum albumin and sodium levels in the heterozygous PRKN variant carriers. These results identify a set of biomarkers that might be useful either individually or as an ensemble to identify variant carriers at greater risk of health issues due to carrier status.

scholarly journals Autonomic Dysfunctions in Parkinson’s Disease: Prevalence, Clinical Characteristics, Potential Diagnostic Markers, and Treatment

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Zhe Zhang ◽  
Sheng-Di Chen
Keyword(s):  
Quality Of Life ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Characteristics ◽  
Treatment Options ◽  
Clinical Manifestations ◽  
The Elderly ◽  
Disease Prevalence ◽  
Autonomic Dysfunctions

Parkinson’s disease (PD) is a common neurodegenerative disease in the middle-aged and the elderly. Symptoms of autonomic dysfunctions are frequently seen in PD patients, severely affecting the quality of life. This review summarizes the epidemiology, clinical manifestations, and treatment options of autonomic dysfunctions. The clinical significance of autonomic dysfunctions in PD early diagnosis and differential diagnosis is also discussed.

Clinical and Dopamine Depletion Patterns in Hyposmia- and Dysautonomia-Dominant Parkinson’s Disease

2021 ◽  
pp. 1-11
Author(s):  
Han Soo Yoo ◽  
Young-gun Lee ◽  
Seong Ho Jeong ◽  
Byoung Seok Ye ◽  
Young H. Sohn ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Characteristics ◽  
Ventral Striatum ◽  
Neuropsychiatric Symptoms ◽  
Age At Onset ◽  
Clinical Manifestations ◽  
Rem Sleep Behavior Disorder ◽  
Dopamine Depletion ◽  
Prodromal Symptoms

Background: Olfactory or autonomic dysfunction is one of the earliest prodromal symptoms of Parkinson’s disease (PD). It has not been investigated whether PD patients have different phenotypes depending on the presence of these prodromal symptoms. Objective: To investigate whether hyposmia-dominant and dysautonomia-dominant patients with early PD have different clinical manifestations and nigrostriatal degeneration. Methods: This cross-sectional study recruited 168 drug-naive PD patients and 34 control subjects. PD patients were classified as patients without hyposmia and dysautonomia (PD–H–D–, n = 51), hyposmia-dominant patients (PD–H+D–, n = 36), dysautonomia-dominant patients (PD–H–D+, n = 33), and patients with hyposmia and dysautonomia (PD–H+D+, n = 48). We then compared the baseline clinical characteristics, striatal specific to non-specific binding ratio (SNBR), neuropsychological performance, and neuropsychiatric symptoms among the groups. Results: The PD–H+D–group had a lower SNBR in the ventral striatum (p = 0.013), a greater asymmetric index of striatal SNBRs, and higher prevalence of apathy (p = 0.021) than the PD–H–D+ group. The PD–H–D+ group had older age at onset (p = 0.043) and a higher prevalence of REM sleep behavior disorder (p = 0.041) than the PD–H+D–group. The PD–H+D+ group had higher motor deficits, lower cognitive function, and lower SNBRs in all striatal subregions than the PD–H–D–group. Decreased SNBRs in the anterior caudate, posterior caudate, and ventral striatum were associated with the presence of apathy. Conclusion: The present study suggests that hyposmia-dominant and dysautonomia-dominant PD have different clinical characteristics and patterns of striatal dopamine depletion.

scholarly journals An Innovative Personalised Management Program for Older Adults with Parkinson’s Disease: New Concepts and Future Directions

2021 ◽  
Vol 11 (1) ◽  
pp. 43
Author(s):  
Piyush Varma ◽  
Lakshanaa Narayan ◽  
Jane Alty ◽  
Virginia Painter ◽  
Chandrasekhara Padmakumar
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Older Persons ◽  
Clinical Manifestations ◽  
Clinical Syndrome ◽  
Management Program ◽  
Older Person ◽  
Care Needs ◽  
Future Directions ◽  
New Concepts

Introduction: Parkinson’s disease is a heterogeneous clinical syndrome. Parkinson’s disease in older persons presents with a diverse array of clinical manifestations leading to unique care needs. This raises the need for the healthcare community to proactively address the care needs of older persons with Parkinson’s disease. Though it is tempting to categorise different phenotypes of Parkinson’s disease, a strong evidence based for the same is lacking. There is considerable literature describing the varying clinical manifestations in old age. This article aims to review the literature looking for strategies in personalising the management of an older person with Parkinson’s disease.

Clinical characteristics of Parkinson's disease in Sudanese patients attending Daoud Charity Clinic in 2020–2021

2021 ◽  
Vol 429 ◽  
pp. 119594
Author(s):  
Radi Tofaha Alhusseini ◽  
Abbasher Hussien ◽  
Khabab Mohamed Ahmed ◽  
Hussien Abbashar ◽  
Amira Abdelgalil ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Characteristics

Different saccadic abnormalities in PINK1 mutation carriers and in patients with non-genetic Parkinson’s disease

2009 ◽  
Vol 256 (7) ◽  
pp. 1192-1194 ◽  
Author(s):  
Susanne Hertel ◽  
Andreas Sprenger ◽  
Christine Klein ◽  
Detlef Kömpf ◽  
Christoph Helmchen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mutation Carriers

scholarly journals Allelic variant in SLC6A3 rs393795 affects cerebral regional homogeneity and gait dysfunction in patients with Parkinson’s disease

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7957
Author(s):  
Lina Wang ◽  
Yongsheng Yuan ◽  
Jianwei Wang ◽  
Yuting Shen ◽  
Yan Zhi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Allelic Variation ◽  
Inferior Frontal Gyrus ◽  
Freezing Of Gait ◽  
Clinical Manifestations ◽  
Regional Homogeneity ◽  
Allelic Variant ◽  
Analysis Of Covariance ◽  
Link Type

Aims We sought to explore the role of the SLC6A3 rs393795 allelic variant in cerebral spontaneous activity and clinical features in Parkinson’s disease (PD) via imaging genetic approach. Methods Our study recruited 50 PD and 45 healthy control (HC) participants to provide clinical, genetic, and resting state functional magnetic resonance imaging (rs-fMRI) data. All subjects were separated into 16 PD-AA, 34 PD-CA/CC, 14 HC-AA, and 31 HC-CA/CC four subgroups according to SLC6A3 rs393795 genotyping. Afterwards, main effects and interactions of groups (PD versus HC) and genotypes (AA versus CA/CC) on cerebral function reflected by regional homogeneity (ReHo) were explored using two-way analysis of covariance (ANCOVA) after controlling age and gender. Finally, Spearman’ s correlations were employed to investigate the relationships between significantly interactive brain regions and clinical manifestations in PD subgroups. Results Compared with HC subjects, PD patients exhibited increased ReHo signals in left middle temporal gyrus and decreased ReHo signals in left pallidum. Compared with CA/CC carriers, AA genotype individuals showed abnormal increased ReHo signals in right inferior frontal gyrus (IFG) and supplementary motor area (SMA). Moreover, significant interactions (affected by both disease factor and allelic variation) were detected in right inferior temporal gyrus (ITG). Furthermore, aberrant increased ReHo signals in right ITG were observed in PD-AA in comparison with PD-CA/CC. Notably, ReHo values in right ITG were negatively associated with Tinetti Mobility Test (TMT) gait subscale scores and positively related to Freezing of Gait Questionnaire (FOG-Q) scores in PD-AA subgroup. Conclusions Our findings suggested that SLC6A3 rs393795 allelic variation might have a trend to aggravate the severity of gait disorders in PD patients by altering right SMA and IFG function, and ultimately result in compensatory activation of right ITG. It could provide us with a new perspective for exploring deeply genetic mechanisms of gait disturbances in PD.

scholarly journals Insights into the multifaceted role of circular RNAs: implications for Parkinson’s disease pathogenesis and diagnosis

2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Epaminondas Doxakis
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Clinical Manifestations ◽  
Alpha Synuclein ◽  
Circular Rnas ◽  
Age Related ◽  
And Function ◽  
The Brain

AbstractParkinson’s disease (PD) is a complex, age-related, neurodegenerative disease whose etiology, pathology, and clinical manifestations remain incompletely understood. As a result, care focuses primarily on symptoms relief. Circular RNAs (circRNAs) are a large class of mostly noncoding RNAs that accumulate with aging in the brain and are increasingly shown to regulate all aspects of neuronal and glial development and function. They are generated by the spliceosome through the backsplicing of linear RNA. Although their biological role remains largely unknown, they have been shown to regulate transcription and splicing, act as decoys for microRNAs and RNA binding proteins, used as templates for translation, and serve as scaffolding platforms for signaling components. Considering that they are stable, diverse, and detectable in easily accessible biofluids, they are deemed promising biomarkers for diagnosing diseases. CircRNAs are differentially expressed in the brain of patients with PD, and growing evidence suggests that they regulate PD pathogenetic processes. Here, the biogenesis, expression, degradation, and detection of circRNAs, as well as their proposed functions, are reviewed. Thereafter, research linking circRNAs to PD-related processes, including aging, alpha-synuclein dysregulation, neuroinflammation, and oxidative stress is highlighted, followed by recent evidence for their use as prognostic and diagnostic biomarkers for PD.

Camptocormia in Idiopathic Parkinson’s Disease: [123I]β-CIT SPECT and Clinical Characteristics

2003 ◽  
Vol 50 (2) ◽  
pp. 118-120 ◽  
Author(s):  
Iris Holler ◽  
Georg Dirnberger ◽  
Walter Pirker ◽  
Eduard Auff ◽  
Willibald Gerschlager
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Characteristics ◽  
Idiopathic Parkinson’S Disease ◽  
Idiopathic Parkinson's Disease

scholarly journals Increased yield of full GBA sequencing in Ashkenazi Jews with Parkinson's disease

2019 ◽  
Vol 62 (1) ◽  
pp. 65-69 ◽  
Author(s):  
Jennifer A. Ruskey ◽  
Lior Greenbaum ◽  
Léanne Roncière ◽  
Armaghan Alam ◽  
Dan Spiegelman ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Ashkenazi Jews
Sign in / Sign up

Export Citation Format

Share Document