PSEN1 G417S mutation in a Chinese pedigree causing early-onset parkinsonism with cognitive impairment.

Presenilin 1 (PSEN1) mutations are a major cause of familial Alzheimer's disease. The pathogenic variant, PSEN1 p.G417S, has been reported to be associated with spastic paraparesis and cotton wool plaques in Japan.

Constructing Prediction Models for Freezing of Gait by Nomogram and Machine Learning: A Longitudinal Study.

Although risk factors for freezing of gait (FOG) have been reported, there are still few prediction models based on cohorts that predict FOG. This 1-year longitudinal study was aimed to identify the clinical measurements closely linked with FOG in Chinese patients with Parkinson's disease (PD) and construct prediction models based on those clinical measurements using Cox regression and machine learning. The study enrolled 967 PD patients without FOG in the Hoehn and Yahr (H&Y) stage 1-3 at baseline.

The Association Between Lysosomal Storage Disorder Genes and Parkinson's Disease: A Large Cohort Study in Chinese Mainland Population.

Recent years have witnessed an increasing number of studies indicating an essential role of the lysosomal dysfunction in Parkinson's disease (PD) at the genetic, biochemical, and cellular pathway levels. In this study, we investigated the association between rare variants in lysosomal storage disorder (LSD) genes and Chinese mainland PD. We explored the association between rare variants of 69 LSD genes and PD in 3,879 patients and 2,931 controls from Parkinson's Disease & Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC) using next-generation sequencing, which were analyzed by using the optimized sequence kernel association test.

Low-frequency and rare coding variants of NUS1 contribute to susceptibility and phenotype of Parkinson's disease.

NUS1 has been recently identified as a candidate gene for Parkinson's disease (PD). Few studies have examined the association of NUS1 variants with PD susceptibility and phenotypes. In the first cohort, whole-exome sequencing was performed to identify variants in NUS1 exon-coding and exon-intron regions in 1542 cases and 1625 controls.

Evaluating the role of ARSA in Chinese patients with Parkinson's disease.

Recent studies have suggested ARSA, a gene responsible for metachromatic leukodystrophy, could be a genetic modifier of Parkinson's disease (PD) pathogenesis, acting as a molecular chaperone for α-synuclein. To elucidate the role of ARSA variants in PD, we did a comprehensive analysis of ARSA variants by performing next-generation sequencing on 477 PD families, 1440 sporadic early-onset PD patients and 1962 sporadic late-onset PD patients and 2636 controls from Chinese mainland, as well as the association between ARSA variants and cognitive function of PD patients. We identified 2 familial PD following autosomal dominant inherence carrying rare variants of ARSA, but they had limited clinical significance.

Contribution of coding/non-coding variants in NUS1 to late-onset sporadic Parkinson's disease.

Introduction: A recent study reported that rare variants in NUS1 were associated with Parkinson's disease (PD). We aimed to assess the relative contribution of rare and common coding/non-coding variants of NUS1 to late-onset PD patients (LOPD).

Methods: Whole genome sequencing data were analyzed for target NUS1 regions, derived from a cohort of 1962 cases and 1279 controls.

Assessment of the association between NUS1 variants and essential tremor.

Background: A recent study on early onset Parkinson's disease (PD) revealed that NUS1 is a risk gene for PD. Clinically, essential tremor (ET) is closely related to PD. In this study, we aimed to detect NUS1 variants and assess the effect of those variants on patients with ET.

GCH1 variants contribute to the risk and earlier age-at-onset of Parkinson's disease: a two-cohort case-control study.

Background: Common and rare variants of guanosine triphosphate cyclohydrolase 1 (GCH1) gene may play important roles in Parkinson's disease (PD). However, there is a lack of comprehensive analysis of GCH1 genotypes, especially in non-coding regions. The aim of this study was to explore the genetic characteristics of GCH1, including rare and common variants in coding and non-coding regions, in a large population of PD patients in Chinese mainland, as well as the phenotypic characteristics of GCH1 variant carriers.

Expansion of GGC repeat in the human-specific NOTCH2NLC gene is associated with essential tremor.

Essential tremor is one of the most common movement disorders. Despite its high prevalence and heritability, the genetic aetiology of essential tremor remains elusive. Up to now, only a few genes/loci have been identified, but these genes have not been replicated in other essential tremor families or cohorts.

Expansion of Human-Specific GGC Repeat in Neuronal Intranuclear Inclusion Disease-Related Disorders.

Neuronal intranuclear inclusion disease (NIID) is a slowly progressing neurodegenerative disease characterized by eosinophilic intranuclear inclusions in the nervous system and multiple visceral organs. The clinical manifestation of NIID varies widely, and both familial and sporadic cases have been reported. Here we have performed genetic linkage analysis and mapped the disease locus to 1p13.

Clinical Features and Correlates of Excessive Daytime Sleepiness in Parkinson's Disease.

To explore the clinical features and correlates of excessive daytime sleepiness (EDS) in a Chinese population of Parkinson's disease (PD) patients. Patients with clinically established or clinically probable PD were recruited. Clinical and demographic data were collected, and participants were evaluated using standardized assessment protocols.

Impaired iPLAβ activity affects iron uptake and storage without iron accumulation: An in vitro study excluding decreased iPLAβ activity as the cause of iron deposition in PLAN.

PLA2G6-associated neurodegeneration (PLAN, NBIA2) is the second most common type of neurodegeneration with brain iron accumulation (NBIA), caused by recessive mutations of PLA2G6 gene, which encodes Ca-independent phospholipase Aβ (iPLAβ). In most PLAN cases, decreased iPLAβ activity and iron deposition was observed meanwhile, and researchers also identified a PLA2G6 mutation family without iron deposition shown by MRI images. This brought us the question of whether decreased iPLAβ activity was the cause of iron deposition in PLAN.

Coding mutations in contribute to Parkinson's disease.

Whole-exome sequencing has been successful in identifying genetic factors contributing to familial or sporadic Parkinson's disease (PD). However, this approach has not been applied to explore the impact of de novo mutations on PD pathogenesis. Here, we sequenced the exomes of 39 early onset patients, their parents, and 20 unaffected siblings to investigate the effects of de novo mutations on PD.

Identification of Ser465 as a novel PINK1 autophosphorylation site.

Background: PINK1 (PTEN-induced putative kinase 1) gene is the causal gene for recessive familial type 6 of Parkinson's disease (PARK6), which is an early-onset autosomal recessive inherited neurodegenerative disease. PINK1 has been reported to exert both autophosphorylation and phosphorylation activity, affecting cell damage under stress and other physiological responses. However, there has been no report on the identification of PINK1 autophosphorylation sites and their physiological functions.

RAB39B gene mutations are not linked to familial Parkinson's disease in China.

Recently, RAB39B mutations were reported to be a causative factor in patients with Parkinson's disease (PD). To validate the role of RAB39B in familial PD, a total of 195 subjects consisting of 108 PD families with autosomal-dominant (AD) inheritance and 87 PD families with autosomal-recessive (AR) inheritance in the Chinese Han population from mainland China were included in this study. We did not identify any variants in the coding region or the exon-intron boundaries of the gene by Sanger sequencing method in the DNA samples of 180 patients (100 with AD and 80 with AR).

The GBA, DYRK1A and MS4A6A polymorphisms influence the age at onset of Chinese Parkinson patients.

Parkinson's disease (PD) is known as the most common neurodegenerative disease after Alzheimer's disease (AD). The precise pathogenic mechanism of PD remains unclear, but genetic and environmental factors are widely recognized to be associated with it. Although many associated genes have been discovered, they account for only a few PD patients.

Relationship between Alzheimer's disease GWAS-linked top hits and risk of Parkinson's disease with or without cognitive decline: a Chinese population-based study.

Alzheimer's disease (AD), Parkinson's disease (PD), and cognitive impairment in PD have overlapping clinical and pathological features. To examine whether there is a genetic link for these diseases, we performed a case-control study in Chinese population to evaluate the association of AD genome-wide association studies top hits with both PD and cognitive function in PD, investigating 13 single-nucleotide polymorphisms in 9 genes (BIN1, CLU, ABCA7, CR1, PICALM, MS4A6A, CD33, MS4A4E, and CD2AP). A total of 454 controls and 442 PD patients were genotyped, including 75 mild cognitive impairment and 99 dementia.

Effect of GBA Mutations on Phenotype of Parkinson's Disease: A Study on Chinese Population and a Meta-Analysis.

GBA has been identified as a genetic risk factor for PD. Whether the clinical manifestations of PD patients with or without GBA mutations are different has still not reached a consensus. We firstly detected the GBA mutation L444P in 1147 Chinese PD patients and simultaneously evaluated their corresponding clinical data.

The contribution of GIGYF2 to Parkinson's disease: a meta-analysis.

The contribution of the gene of GIGYF2, Grb10-Interacting GYF Protein 2, to Parkinson's disease (PD) is still ambiguous. To explore the contribution of GIGYF2 to PD at the genetic level, we analyzed the relationship between all reported GIGYF2 variants (including mutations and polymorphisms) and PD through a meta-analysis. Databases including Medline, Embase, etc.