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Journal of the Formosan Medical... Jan 2022A heterozygous three-nucleotide (GAG) in-frame deletion in the TOR1A gene causes the rare disease, dystonia (DYT1), which typically presents as focal limb dystonia...
BACKGROUND/PURPOSE
A heterozygous three-nucleotide (GAG) in-frame deletion in the TOR1A gene causes the rare disease, dystonia (DYT1), which typically presents as focal limb dystonia during adolescence, then spreads to other limbs. This study investigated the frequency and clinical features of DYT1 in a Taiwanese dystonia cohort.
METHODS
We performed targeted next generation sequencing in 318 patients with primary dystonia. We identified one DYT1 family with various types of dystonia, and we described the clinical presentations observed in this family during a 30-year follow-up. We compared the clinical characteristics to those reported in previous studies on DYT1 from 2000 to 2020.
RESULTS
Among 318 patients, we identified only one DYT1 patient (0.3%) with an autosomal dominant family history of dystonia. The proband was a 43-year-old man that experienced progressive onset of focal lower limb dystonia from age 11 years. The disease spread caudal-rostrally to the upper limbs and cervical muscles. Prominent cervical dystonia was noted during follow-up, which was an atypical presentation of DYT1. Clinical assessments of other family members showed intrafamily variability. The proband's father and an affected sibling demonstrated only mild right-hand writer's cramp. A systematic review of previously reported DTY1 cases showed that Asian patients had a higher frequency of cervical dystonia (44.8%) than groups of Ashkenazi Jews (35%) and Non-Jewish Caucasians (30.5%) (P = 0.04).
CONCLUSION
Our findings revealed that DYT1 is rare in a Taiwanese dystonia cohort. The presentation of marked cervical dystonia could be the main feature of Asian patients with DYT1.
Topics: Adult; Child; Dystonic Disorders; Genetic Diseases, X-Linked; Humans; Male; Molecular Chaperones; Taiwan
PubMed: 34092466
DOI: 10.1016/j.jfma.2021.05.017 -
International Journal of Medical... 2021Although high-mobility group box 1 and heat-shock protein 70 are implicated in airway diseases and suggested as relevant diagnostic biomarkers, their control... (Meta-Analysis)
Meta-Analysis
Although high-mobility group box 1 and heat-shock protein 70 are implicated in airway diseases and suggested as relevant diagnostic biomarkers, their control concentrations in the airways have not yet been determined. This study aimed to evaluate concentration of healthy subjects for both these proteins in the upper and lower airways via meta-analysis. We searched MEDLINE, EMBASE, and Google Scholar for articles describing concentration of healthy subjects for these proteins. Data from healthy populations were combined using a random-effects model, and subgroup and sensitivity analyses were performed to determine between-study heterogeneity. We analyzed 22 studies involving 485 patients. Concentration of healthy subjects of high-mobility group box 1 and heat-shock protein 70 varied from "not detected" to 326.13 ng/mL and from 0.20 pg/mL to 9240.00 pg/mL, respectively, with the values showing significant heterogeneity. Subgroup analysis for high-mobility group box 1 revealed 13.63 ng/mL (95% CI 12.13-15.14), 100.31 ng/mL (95% CI -31.28-231.91), 9.54 ng/mL (95% CI 8.91-10.17), and 65.82 ng/mL (95% CI 55.51-76.14) for the lower airway, upper airway, pediatric populations, and adults, respectively, whereas that for heat-shock protein 70 revealed 20.58 pg/mL (95% CI 7.87-33.29) for the lower airway and 9240.00 ±11820 pg/mL for the upper airway. Although concentrations of healthy subjects of these proteins varied in the upper and lower airways, the levels of both these proteins were higher in the upper airway than in the lower airway, and these concentrations differed according to the age and sampling procedure. Our findings support the further evaluation of these proteins as biomarkers for airway-related diseases.
Topics: Biomarkers; HMGB1 Protein; HSP70 Heat-Shock Proteins; Healthy Volunteers; Humans; Reference Values; Respiratory Mucosa
PubMed: 33746593
DOI: 10.7150/ijms.53500 -
Medicine Jan 2021Heat-shock proteins (HSP) is a key chaperone protein which maintains intracellular proteostasis and is expressed on the surface of solid and hematological malignancies.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Heat-shock proteins (HSP) is a key chaperone protein which maintains intracellular proteostasis and is expressed on the surface of solid and hematological malignancies. Several studies have reported paradoxical evidence of the association between HSP expression and prognosis of oral cancer. To address the discrepancy, we carried out the meta-analysis to assess the role of HSP such as: HSP70, HSP90, HSP27, HSP60, and HSP105 in susceptibility, progression, and prognosis of oral cancer.
MATERIALS AND METHODS
We retrieved the PubMed, Embase, Web of science, China National Knowledge Infrastructure (CNKI), and Wanfang databases to acquire the eligible studies which were associated with HSP70, HSP90, HSP27, HSP60, and HSP105 protein expression and oral cancer. We applied hazard ratio (HR) and its 95% confidence interval (95% CI) to assess the value of HSP protein expression in overall survival of oral cancer; odds ratio (OR) and its 95% CI were used to evaluate the association of risk and clinical features of oral cancer. Funnel plot, Begg test, and Egger line regression test were utilized to observe publication bias among studies. All statistical analysis was performed with Stata 14.0 software (Stata Corporation, College Station, TX).
RESULTS
A total of 26 studies were included in the present meta-analysis. On based of the results, HSP70 and HSP27 had no significant association with progression of oral cancer. However, the pooled HR and 95% CI revealed a significant well effects of HSP70 and HSP27 expression on survival of oral cancer. Moreover, the susceptibility of oral cancer was significantly associated with HSP70 and HSP60 overexpression.
CONCLUSION
HSP70 and HSP27 protein overexpression might be valuable biomarkers for the prognosis of oral cancer. And HSP70 and HSP60 might have potential predictive effects on the risk of oral cancer.
Topics: HSP70 Heat-Shock Proteins; Heat-Shock Proteins; Humans; Mouth Neoplasms; Prognosis; Proportional Hazards Models
PubMed: 33546049
DOI: 10.1097/MD.0000000000024274 -
Movement Disorders : Official Journal... May 2021This comprehensive MDSGene review is devoted to 7 genes - TOR1A, THAP1, GNAL, ANO3, PRKRA, KMT2B, and HPCA - mutations in which may cause isolated dystonia. It followed... (Review)
Review
This comprehensive MDSGene review is devoted to 7 genes - TOR1A, THAP1, GNAL, ANO3, PRKRA, KMT2B, and HPCA - mutations in which may cause isolated dystonia. It followed MDSGene's standardized data extraction protocol and screened a total of ~1200 citations. Phenotypic and genotypic data on ~1200 patients with 254 different mutations were curated and analyzed. There were differences regarding age at onset, site of onset, and distribution of symptoms across mutation carriers in all 7 genes. Although carriers of TOR1A, THAP1, PRKRA, KMT2B, or HPCA mutations mostly showed childhood and adolescent onset, patients with GNAL and ANO3 mutations often developed first symptoms in adulthood. GNAL and KMT2B mutation carriers frequently have 1 predominant site of onset, that is, the neck (GNAL) or the lower limbs (KMT2B), whereas site of onset in DYT-TOR1A, DYT-THAP1, DYT-ANO3, DYT-PRKRA, and DYT-HPCA was broader. However, in most DYT-THAP1 and DYT-ANO3 patients, dystonia first manifested in the upper half of the body (upper limb, neck, and craniofacial/laryngeal), whereas onset in DYT-TOR1A, DYT-PRKRA and DYT-HPCA was frequently observed in an extremity, including both upper and lower ones. For ANO3, a segmental/multifocal distribution was typical, whereas TOR1A, PRKRA, KMT2B, and HPCA mutation carriers commonly developed generalized dystonia. THAP1 mutation carriers presented with focal, segmental/multifocal, or generalized dystonia in almost equal proportions. GNAL mutation carriers rarely showed generalization. This review provides a comprehensive overview of the current knowledge of hereditary isolated dystonia. The data are also available in an online database (http://www.mdsgene.org), which additionally offers descriptive summary statistics. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Adolescent; Adult; Anoctamins; Apoptosis Regulatory Proteins; Child; DNA-Binding Proteins; Dystonia; Dystonic Disorders; Genotype; Humans; Molecular Chaperones; Mutation; Phenotype
PubMed: 33502045
DOI: 10.1002/mds.28485 -
Medicina (Kaunas, Lithuania) Dec 2020Heat shock protein 90 (Hsp90) is a molecular chaperone that plays an essential role in tumor growth. Numerous Hsp90 inhibitors have been discovered and tested in... (Meta-Analysis)
Meta-Analysis Review
Heat shock protein 90 (Hsp90) is a molecular chaperone that plays an essential role in tumor growth. Numerous Hsp90 inhibitors have been discovered and tested in preclinical and clinical trials. Recently, several preclinical studies have demonstrated that Hsp90 inhibitors could modulate pain sensitization. However, no studies have evaluated the impact of Hsp90 inhibitors on pain in the patients. This study aims to summarize the pain events reported in clinical trials assessing Hsp90 inhibitors and to determine the effect of Hsp90 inhibitors on pain in patients. We searched PubMed, EBSCOhost, and clinicaltrials.gov for Hsp90 inhibitor clinical trials. The pain-related adverse events were summarized. Meta-analysis was performed using the data reported in randomized controlled trials. We identified 90 clinical trials that reported pain as an adverse effect, including 5 randomized controlled trials. The most common types of pain reported in all trials included headache, abdominal pain, and back pain. The meta-analysis showed that Hsp90 inhibitors increased the risk of abdominal pain significantly and appeared to increase the risk for back pain. In conclusion, Hsp90 inhibitor treatment could potentially increase the risk of pain. However, the meta-analysis demonstrated only moderate evidence for the connection between Hsp90 inhibitor and pain.
Topics: Antineoplastic Agents; Cancer Pain; HSP90 Heat-Shock Proteins; Humans; Neoplasms
PubMed: 33374669
DOI: 10.3390/medicina57010005 -
Molecular Biology Reports Jan 2021Mutations in Lysine-Specific Histone Methyltransferase 2B gene (KMT2B) have been reported to be associated with isolated and complex early-onset generalized dystonia. We... (Meta-Analysis)
Meta-Analysis
Mutations in Lysine-Specific Histone Methyltransferase 2B gene (KMT2B) have been reported to be associated with isolated and complex early-onset generalized dystonia. We describe clinico-genetic features on a Greek patient with a novel de novo variant and demonstrate the phenotypic spectrum of KMT2B variants. We performed whole exome sequencing (WES), in a Greek patient with sporadic generalized dystonia. Additionally, we performed a systematic review of all published cases with KMT2B variants. The patient presented with isolated and mild generalized dystonia. We identified a novel splice site variant that was confirmed by Sanger sequencing and was not found in parents. This is the first reported KMT2B variant, in the Greek population. This case report further highlights the growing trend of identifying genetic diseases previously restricted to few cases in many different ethnic groups worldwide via exome sequencing. In the systematic review, we evaluated the mutation pathogenicity in all previously reported cases to investigate possible phenotype-genotype correlations. Greater mutation numbers in different populations will be important and mutation-specific functional studies will be essential to identify the pathogenicity of the various KMT2B variants.
Topics: Adult; Age of Onset; Dystonia; Exome; Female; Genetic Association Studies; Greece; Histone-Lysine N-Methyltransferase; Histones; Humans; Male; Molecular Chaperones; Mutation; Pedigree; Phenotype; Protein Isoforms; Exome Sequencing
PubMed: 33300088
DOI: 10.1007/s11033-020-06057-3 -
Frontiers in Physiology 2020Glucocerebrosides are sphingolipid components of cell membranes that intervene in numerous cell biological processes and signaling pathways and that deregulation is...
Glucocerebrosides are sphingolipid components of cell membranes that intervene in numerous cell biological processes and signaling pathways and that deregulation is implicated in human diseases such as Gaucher disease and Parkinson's disease. In the present study, we conducted a systematic review using document co-citation analysis, clustering and visualization tools to explore the trends and knowledge structure of glucocerebrosides research as indexed in the Science Citation Index Expanded database (1956-present). A co-citation network of 5,324 publications related to glucocerebrosides was constructed. The analysis of emerging categories and keywords suggested a growth of research related to neurosciences over the last decade. We identified ten major areas of research (e.g., clusters) that developed over time, from the oldest (i.e., on or ) to the most recent ones (i.e., on , or ). We provided for each cluster the most cited publications and a description of their intellectual content. We moreover identified emerging trends in glucocerebrosides research by detecting the surges in the rate of publication citations in the most recent years. In conclusion, this study helps to apprehend the most significant lines of research on glucocerebrosides. This should strengthen the connections between scientific communities studying glycosphingolipids to facilitate advances, especially for the most recent researches on cancer drug resistance and Parkinson's disease.
PubMed: 33192552
DOI: 10.3389/fphys.2020.558090 -
European Journal of Neurology Apr 2021We aimed to investigate the prevalence of TOR1A, GNAL and THAP1 variants as the cause of dystonia in a cohort of Spanish patients with isolated dystonia and in the...
OBJECTIVE
We aimed to investigate the prevalence of TOR1A, GNAL and THAP1 variants as the cause of dystonia in a cohort of Spanish patients with isolated dystonia and in the literature.
METHODS
A population of 2028 subjects (including 1053 patients with different subtypes of isolated dystonia and 975 healthy controls) from southern and central Spain was included. The genes TOR1A, THAP1 and GNAL were screened using a combination of high-resolution melting analysis and direct DNA resequencing. In addition, an extensive literature search to identify original articles (published before 10 August 2020) reporting mutations in TOR1A, THAP1 or GNAL associated to dystonia was performed.
RESULTS
Pathogenic or likely pathogenic variants in TOR1A, THAP1 and GNAL were identified in 0.48%, 0.57% and 0.29% of our patients, respectively. Five patients carried the variation p.Glu303del in TOR1A. A very rare variant in GNAL (p.Ser238Asn) was found as a putative risk factor for dystonia. In the literature, variations in TOR1A, THAP1 and GNAL accounted for about 6%, 1.8% and 1.1% of published dystonia patients, respectively.
CONCLUSIONS
There is a different genetic contribution to dystonia of these three genes in our patients (about 1.3% of patients) and in the literature (about 3.6% of patients), probably due the high proportion of adult-onset cases in our cohort. As regards age at onset, site of dystonia onset, and final distribution, in our population there is a clear differentiation between DYT-TOR1A and DYT-GNAL, with DYT-THAP1 likely to be an intermediate phenotype.
Topics: Adult; Apoptosis Regulatory Proteins; DNA-Binding Proteins; Dystonia; Dystonic Disorders; Humans; Molecular Chaperones; Mutation; Spain
PubMed: 33175450
DOI: 10.1111/ene.14638 -
Journal of the Peripheral Nervous... Sep 2020Mutations in the HSPB1 gene are associated with Charcot-Marie-Tooth (CMT) disease type 2F (CMT2F) and distal hereditary motor neuropathy type 2 (dHMN2). More than 18... (Review)
Review
Mutations in the HSPB1 gene are associated with Charcot-Marie-Tooth (CMT) disease type 2F (CMT2F) and distal hereditary motor neuropathy type 2 (dHMN2). More than 18 pathogenic mutations spanning across the whole HSPB1 gene have been reported. Three family members with a novel p.P57S (c.169C>T) HSPB1 mutation resulting in a late onset axonal neuropathy with heterogeneous clinical and electrophysiological features are detailed. We systematically reviewed published case reports and case series on HSPB1 mutations. While a genotype-phenotype correlation was not obvious, we identified a common phenotype, which included adult onset, male predominance, motor more frequently than sensory involvement, distal and symmetric distribution with preferential involvement of plantar flexors, and a motor and axonal electrophysiological picture.
Topics: Age of Onset; Aged; Aged, 80 and over; Charcot-Marie-Tooth Disease; Female; Genetic Association Studies; Heat-Shock Proteins; Humans; Male; Molecular Chaperones; Pedigree
PubMed: 32639100
DOI: 10.1111/jns.12395 -
Journal of Plastic, Reconstructive &... Sep 2020Optimising patients pre-operatively reduces the chance of complications. This may be achieved by preconditioning. Thermal preconditioning refers to the...
BACKGROUND
Optimising patients pre-operatively reduces the chance of complications. This may be achieved by preconditioning. Thermal preconditioning refers to the supraphysiological heating of organisms or specific organs prior to an environmental insult. This review explores the current application and efficacy of thermal preconditioning for surgery.
METHODS
A comprehensive search of Medline (via PubMed), Embase and the Cochrane library was performed. Only articles evaluating the use of supraphysiological heating prior to a surgical intervention were included. Qualitative syntheses of data were undertaken due to the heterogeneity of the studies. The quality of each article was appraised using risk of bias tools (Cochrane and SYRCLE).
RESULTS
The primary literature search returned 3175 articles. After screening and reviewing reference lists, 28 papers met the inclusion criteria. The majority of studies were performed in animals, with only three clinical trials. Although there was broad coverage of different surgical techniques, flap transfer was the most commonly performed procedure. Most studies demonstrated a beneficial effect of thermal preconditioning, ranging from increased joint mobility to improved flap or organ transplant survival rates. The quality of evidence was variable, with experimental animal studies limited by a lack of methodological detail.
CONCLUSIONS
Thermal preconditioning for surgery has been primarily investigated using animal models. A beneficial effect has been demonstrated in most cases, across specialties ranging from plastic to general surgery. Future studies should aim to assess the clinical significance through large multicentre randomised controlled trials.
Topics: Animals; Graft Survival; Heat-Shock Proteins; Heating; Humans; Hypothermia; Intraoperative Complications; Postoperative Complications; Preoperative Care; Surgical Flaps; Surgical Procedures, Operative
PubMed: 32505626
DOI: 10.1016/j.bjps.2020.05.025