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Increasing evidence indicates a strong association between rapid eye movement sleep behavior disorder (RBD) and Parkinson's disease - cognitive impairment (PD-CI). Numerous longitudinal and cross-sectional studies have shown that RBD may be an important risk factor and predictor of Parkinson's disease - mild cognitive impairment (PD-MCI) and Parkinson's disease dementia (PDD); which may be explained by the association of mechanisms between RBD and PD-CI, including neurotransmitter alterations, genetic mutation, neuroinflammation, alpha-synuclein inclusion, abnormal cerebral metabolism and cortical activity slowing. Understanding the role of RBD in cognition of PD, we may predict and prevent the presence of PD-CI. The purpose of our comprehensive narrative review was to investigate the role of RBD in cognition of PD patients and its possible mechanism with lights from clinical epidemiological evidence, neuroimaging and electrophysiology studies. [ABSTRACT FROM AUTHOR]

Background: Paroxysmal kinesigenic dyskinesia is the most common type of paroxysmal dyskinesia. Approximately half of the cases of paroxysmal kinesigenic dyskinesia worldwide are attributable to proline-rich transmembrane protein 2 mutations.Objective: The objective of this study was to investigate potential causative genes and clinical characteristics in proline-rich transmembrane protein 2-negative patients with paroxysmal kinesigenic dyskinesia.Methods: We analyzed clinical manifestations and performed exome sequencing in a cohort of 163 proline-rich transmembrane protein 2-negative probands, followed by filtering data with a paroxysmal movement disorders gene panel. Sanger sequencing, segregation analysis, and phenotypic reevaluation were used to substantiate the findings.Results: The clinical characteristics of the enrolled 163 probands were summarized. A total of 39 heterozygous variants were identified, of which 33 were classified as benign, likely benign, and uncertain significance. The remaining 6 variants (3 novel, 3 documented) were pathogenic and likely pathogenic. Of these, 3 were de novo (potassium calcium-activated channel subfamily M alpha 1, c.1534A>G; solute carrier family 2 member 1, c.418G>A; sodium voltage-gated channel alpha subunit 8, c.3640G>A) in 3 sporadic individuals, respectively. The other 3 (paroxysmal nonkinesiogenic dyskinesia protein, c.956dupA; potassium voltage-gated channel subfamily A member 1, c.765C>A; Dishevelled, Egl-10, and Pleckstrin domain containing 5, c.3311C>T) cosegregated in 3 families. All 6 cases presented with typical paroxysmal kinesigenic dyskinesia characteristics, except for the Dishevelled, Egl-10, and Pleckstrin domain containing 5 family, where the proband's mother had abnormal discharges in her temporal lobes in addition to paroxysmal kinesigenic dyskinesia episodes.Conclusions: Our findings extend the genotypic spectrum of paroxysmal kinesigenic dyskinesia and establish the associations between paroxysmal kinesigenic dyskinesia and genes classically related to other paroxysmal movement disorders. De novo variants might be a cause of sporadic paroxysmal kinesigenic dyskinesia. © 2018 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

As an important multifunctional protein involved in regulation of mitochondrial metabolism, CHCHD2 was identified as a causative gene for Parkinson's disease (PD), yet the relationship between CHCHD2 and neurodegenerative dementia is not well understood. We directly sequenced the entire coding region of CHCHD2 gene in 150 AD patients, 84 FTD patients, and 417 controls. Four rare putative pathogenic variants of CHCHD2, including rs142444896 (c.5C>T, p.P2L), rs752705344 (c.15C>G, p.S5R), rs145190179 (c.94G>A, p.A32T), and rs182992574 (c.255T>A, p.S85R) were identified from a cohort composed of 150 AD and 84 FTD patients. These results suggest that CH CHD2 gene play an important role in other neurodegenerative disorders from our dementia study in China. [ABSTRACT FROM AUTHOR]

Background: Huntington's disease (HD) is an autosomal dominant disorder, typically characterized by chorea due to a trinucleotide repeat expansion in the HTT gene, although the clinical manifestations of patients with juvenile HD (JHD) are atypical.Case Presentation: A 17-year-old boy with initial presentation of tics attended our clinic and his DNA analysis demonstrated mutation in the HTT gene (49 CAG repeats). After treatment, his symptoms improved. Furthermore, we performed literature review through searching the databases and summarized clinical features in 33 JHD patients.Conclusion: The most prevalent symptoms are ataxia, and two cases reported that tics as initial and prominent manifestation in JHD. Among them, 88% patients carried CAG repeats beyond 60 and most of them have family history. This case here illustrates the variable range of clinical symptoms of JHD and the necessity of testing for the HD mutation in young patients with tics with symptoms unable to be explained by Tourette's syndrome (TS). [ABSTRACT FROM AUTHOR]

Mitochondria play an important role in the etiology of Parkinson’s disease (PD). While mutations in the mitochondrial DNA (mtDNA) have been shown to accumulate in PD, no specific mtDNA polymorphisms have been associated with susceptibility or resistance to PD. A cytosine to adenine transversion at base pair 5178 in the mtDNA has been associated with increased longevity and resistance against a number of age related disorders and has been shown to decrease mitochondrial reactive oxygen species (ROS) production. We sought to determine whether 5178A is associated with resistance against PD in a Han Chinese population. To assess its association with PD, we genotyped 484 idiopathic PD patients and 710 control individuals for 5178C/A. Genotyping was performed using restriction fragment length polymorphism (RFLP) analysis. There was no significant association between 5178A and PD ( P = 0.308) when analyzing the entire population. However, sub-group analysis revealed that in males the frequency of 5178A was significantly lower in PD patients (27.7% in controls vs 20.0% in PD patients, P = 0.027). Stratification of the population by age showed that this trend held across age groups but only reached statistical significance in males aged 60–70 (29.1% in controls vs 14.05 in PD patients, P = 0.011). In conclusion, we demonstrated that the frequency of 5178A was significantly decreased in male PD patients in a Han Chinese population. This polymorphism may be associated with resistance against the development of PD when in combination with loci on the Y chromosome. [ABSTRACT FROM AUTHOR]

Abstract: Background: Hereditary Spastic Paraplegia Type 35 is a complicated form of HSP characterized by progressive spastic paraparesis, dysarthria, and mild cognitive decline associated with leukodystrophy on brain imaging. Mutations in the fatty acid 2-hydroxylase (FA2H) gene have been associated SPG35. Methods: Sequencing of FA2H gene was conducted in a Chinese non-consanguineous family with two affected siblings manifesting with typical clinical features of SPG 35. 100 healthy individuals were set for control. Result: Triple heterozygous mutations in FA2H gene (c.968C>A; c.976G>A; c.688G>A) were identified in the two affected siblings. All the mutations were not documented previously and were not detected among 100 healthy controls. Conclusion: In this study we identified the first SPG 35 family in Han population. Triple FA2H mutations seem to result in a severe phenotype while more patients are needed to establish the genotype–phenotype correlations. [Copyright &y& Elsevier]

Abstract: Background: Hereditary spastic paraplegia is a clinically and genetically heterogeneous neurodegenerative disorder characterized by progressive spasticity of the lower limbs. Mutations in SPG11 gene have been recently identified as a major cause of hereditary spastic paraplegia with thin corpus callosum. Methods: Two unrelated Chinese families were examined by clinical evaluation, mutation analysis of SPG11, detailed neuropsychological assessment and diffusion tensor imaging. Results: Both patients presented with spastic paraparesis and learning disability. Two novel and one known mutations in SPG11 were detected through genetic analysis. Cognitive impairment was found with severe deficits in domains such as executive functions and memory. Magnetic resonance imaging showed thin corpus callosum while diffusion tensor imaging revealed increased mean diffusion and decreased fractional anisotropy in the corpus callosum and subcortical white matter in frontal, temporal lobe compared with the healthy controls. Conclusions: This study widens the spectrum of mutations in SPG11. The application of detailed neuropsychological tests and diffusion tensor imaging could detect cerebral subtle involvement even in early stage of the disease. [Copyright &y& Elsevier]

Abstract: Introduction: Genetic studies restricted to young adult ischemic stroke patients may help in excluding the potentially confounding variables encountered with advanced age; thus, allowing a more precise risk evaluation derived from the inherited mutations alone. Through meta-analysis, this study was conducted to determine the genetic risk contributed by each susceptibility gene polymorphism, particularly in adult early-onset ischemic stroke patients. Materials and Methods: Electronic databases were searched for all the case-control studies relating to any candidate genes for ischemic stroke. The range of age was 18–50 years for cases. Fixed or random effects model was used depending on the heterogeneity between studies. Results: Twenty-six studies were finally included in this meta-analysis; these studies focused on 7 candidate genes. A significant but modest association was identified for 2 polymorphisms, namely, methylenetetrahydrofolate reductase (MTHFR) C677T (OR=1.44, 95% CI=1.14–1.80) and apolipoprotein E (ApoE) ε2–4 (OR=2.53, 95% CI=1.71–3.73). Although the pooled analysis for platelet glycoprotein Ia (GPIa) C807T showed a positive association (OR=1.50, 95% CI=1.10–2.05), the Egger''s test indicated the existence of publication bias (t =5.27, P>|t|=0.034). Conclusions: Genetic abnormalities specific to homocysteine and lipid metabolism increase the risk for ischemic stroke at an early age. These data may offer important implications for future genetic association studies for stroke. [Copyright &y& Elsevier]

Abstract: Grb10-Interacting GYF Protein-2 gene (GIGYF2) has been suggested as a candidate gene for PARK11 locus since seven different GIGYF2 missense mutations were identified in familial Parkinson''s disease (PD) patients of European descent. To evaluate the frequency and distribution of GIGYF2 Asn56Ser mutation in Chinese PD patients, we analyzed 469 patients with PD from mainland China, including 36 cases with familial PD and 433 cases with sporadic PD. A total of 451 subjects without neurological disorders from the same region in China were set as a control group. The result showed that the GIGYF2 Asn56Ser mutation was not present in all subjects. Our finding suggests that the GIGYF2 Asn56Ser mutation is rare in Chinese PD patients. [Copyright &y& Elsevier]

Abstract: Vacuolar protein sorting 35 (VPS35) Asp620Asn mutation has been identified in late-onset familial Parkinson''s disease (PD) patients of Swiss and Austrian descent as well as sporadic PD patients in the United States. In order to determine the contribution of VPS35 mutations in mainland Chinese PD patients and to better understand the association between VPS35 and PD, we sequenced all 17 exons of VPS35 in 32 probands of presumed autosomal-dominant, late-onset familial PD and 35 normal controls. Meanwhile, we analyzed VPS35 Asp620Asn mutation in 512 PD patients. A total of 371 subjects without neurological disorders from the same region in China were set as a control group. We did not find any VPS35 coding region mutation in 32 familial PD patients. VPS35 Asp620Asn mutation was either not found in 480 PD patients. Our results suggested that VPS35 Asp620Asn may be not associated with PD in Chinese population. [Copyright &y& Elsevier]

Abstract: ATP13A2 (PARK9) mutations are related to Kufor-Rakeb syndrome (KRS). We performed genetic analysis of the Ala746Thr variant in an independent cohort of the patients with PD and healthy controls from mainland China. The Ala746Thr variant was present in 1/532 (0.19%) of PD compared with 1/480 (0.21%) of healthy controls (odds ratio=0.90, 95% CI 0.06, 14.39, P =1.00). The two subjects carried the heterozygous genotype. Subset analysis in the group ≤50 years of age revealed a prevalence of 0.7% in PD compared with 0% in healthy controls and in the group >50 years of age showed 0% in PD versus 0.3% in healthy controls. We did not observe a significant association between Ala746Thr and Parkinson''s disease in Han Chinese population, even after stratification by age at onset. The results suggested that Ala746Thr variant was not a major susceptible factor for PD in Han Chinese people. [Copyright &y& Elsevier]

CHCHD2 is the latest identified Parkinson's disease (PD)-causing gene, and previous studies have reported the same CHCHD2 variant (182C>T, Thr61Ile) in both PD and essential tremor (ET) patients. Whether CHCHD2 gene mutations are involved in both of these diseases remains unclear. We sequenced CHCHD2 gene in 171 familial ET patients, 133 autosomal dominant Parkinson's disease patients, and 211 normal controls. No pathogenic mutations were found, suggesting that CHCHD2 gene may not play a major role in our familial Chinese Han ET and PD patients. [ABSTRACT FROM AUTHOR]

Abstract: Recently, the angiogenin gene has been reported to be significantly associated with Parkinson''s disease and amyotrophic lateral sclerosis in populations of European and American ancestry. But there have been no studies investigating the association between angiogenin and Parkinson''s disease in the ethnic Chinese population. We conducted a case–control study to evaluate the association between angiogenin and Parkinson''s disease in a Chinese population from mainland China. We sequenced the exons of angiogenin in 532 Parkinson''s disease patients and 480 controls. We did not detect an angiogenin coding region mutation in either the patients or the controls. Our data do not support the association of angiogenin variants with PD in Han Chinese of mainland China. [Copyright &y& Elsevier]