scholarly journals Genetic Characteristics and Transcriptional Regulation of Sodium Channel Related Genes in Chinese Patients With Brugada Syndrome

2021 ◽  
Vol 8 ◽  
Author(s):  
Ziguan Zhang ◽  
Hongwei Chen ◽  
Wenbo Chen ◽  
Zhenghao Zhang ◽  
Runjing Li ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Brugada Syndrome ◽  
Southern China ◽  
Gene Mutations ◽  
Northern China ◽  
Chinese Patients ◽  
Α Subunit ◽  
Genetic Characteristics ◽  
C Terminus ◽  
Scn5a Gene

Objective: To investigate the genetic characteristics and transcriptional regulation of the SCN5A gene of Brugada syndrome (BrS) patients in China.Methods: Using PubMed, Medline, China National Knowledge Internet (CNKI), and Wanfang Database, Chinese patients with BrS who underwent SCN5A gene testing were studied.Results: A total of 27 suitable studies involving Chinese BrS patients who underwent the SCN5A gene test were included. A total of 55 SCN5A gene mutations/variations were reported in Chinese BrS patients, including 10 from southern China and 45 from northern China. Mutations/variations of BrS patients from southern China mostly occurred in the regions of the α-subunit of Nav1.5, including DIII (Domain III), DIV, DIII-DIV, C-terminus regions, and the 3'UTR region. Furthermore, we analyzed the post-transcriptional modifications (PTMs) throughout the Nav1.5 protein encoded by SCN5A and found that the PTM changes happened in 72.7% of BrS patients from southern China and 26.7% from northern China.Conclusions: SCN5A mutations/variations of BrS patients in southern China mostly occurred in the DIII-DIV to C-terminus region and the 3'-UTR region of the SCN5A gene, different from northern China. PTM changes were consistent with the mutation/variation distribution of SCN5A, which might be involved in the regulation of the pathogenesis of BrS patients.

scholarly journals Development of revised diagnostic criteria for Fuchs’ uveitis syndrome in a Chinese population

2021 ◽  
pp. bjophthalmol-2021-319343
Author(s):  
Peizeng Yang ◽  
Wanyun Zhang ◽  
Zhijun Chen ◽  
Han Zhang ◽  
Guannan Su ◽  
...  
Keyword(s):  
Diagnostic Criteria ◽  
Clinical Symptoms ◽  
Southern China ◽  
High Sensitivity ◽  
Northern China ◽  
Chinese Patients ◽  
Tertiary Referral Centre ◽  
Tree Algorithms ◽  
Vitreous Opacities ◽  
Fuchs Uveitis Syndrome

Background/aimsFuchs’ uveitis syndrome (FUS) is one of the frequently misdiagnosed uveitis entities, which is partly due to the absence of internationally recognised diagnostic criteria. This study was performed to develop and evaluate a set of revised diagnostic criteria for FUS.MethodsThe clinical data of Chinese patients with FUS and patients with non-FUS were collected and analysed from a tertiary referral centre between April 2008 and December 2020. A total of 593 patients with FUS and 625 patients with non-FUS from northern China were enrolled for the development of diagnostic criteria for FUS. Three hundred and seventy-seven patients with FUS and 503 patients with non-FUS from southern China were used to validate the criteria. Clinical symptoms and ocular signs were collected from all patients with FUS and patients with non-FUS. Multivariate two-step cluster analysis, logistic regression and decision tree algorithms in combination with the clinical judgement of uveitis experts were used to revise diagnostic criteria for FUS.ResultsThree essential findings including diffuse iris depigmentation, absence of posterior synechiae, mild inflammation in the anterior chamber at presentation and five associated findings including mostly unilateral involvement, cataract, vitreous opacities, absence of acute symptoms and characteristic iris nodules were used in the development of FUS diagnostic criteria. All essential findings were required for the diagnosis of FUS, and the diagnosis was further strengthened by the presence of associated findings.ConclusionRevised diagnostic criteria for FUS were developed and validated by analysing data from Chinese patients and showed a high sensitivity (96.55%) and specificity (97.42%).

scholarly journals Compound heterozygous SCN5A gene mutations in asymptomatic Brugada syndrome child

2012 ◽  
Vol 2 (1) ◽  
pp. 11 ◽  
Author(s):  
Elena Sommariva ◽  
Matteo Vatta ◽  
Yutao Xi ◽  
Simone Sala ◽  
Tomohiko Ai ◽  
...  
Keyword(s):  
Brugada Syndrome ◽  
Gene Mutations ◽  
Compound Heterozygous ◽  
Scn5a Gene ◽  
Syndrome Child

scholarly journals Epidural Analgesia with Ropivacaine during Labour in a Patient with a SCN5A Gene Mutation

2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
A. L. M. J. van der Knijff-van Dortmont ◽  
M. Dirckx ◽  
J. J. Duvekot ◽  
J. W. Roos-Hesselink ◽  
A. Gonzalez Candel ◽  
...  
Keyword(s):  
Case Report ◽  
Adverse Events ◽  
Epidural Analgesia ◽  
Brugada Syndrome ◽  
Low Dose ◽  
Gene Mutations ◽  
Pregnant Patient ◽  
Cardiac Conduction ◽  
Conduction Disturbances ◽  
Scn5a Gene

SCN5A gene mutations can lead to ion channel defects which can cause cardiac conduction disturbances. In the presence of specific ECG characteristics, this mutation is called Brugada syndrome. Many drugs are associated with adverse events, making anesthesia in patients with SCN5A gene mutations or Brugada syndrome challenging. In this case report, we describe a pregnant patient with this mutation who received epidural analgesia using low dose ropivacaine and sufentanil during labour.

scholarly journals Role of SCN5A coding and non-coding sequences in Brugada syndrome onset: What’s behind the scenes?

2017 ◽  
Author(s):  
Houria Daimi ◽  
Amel Haj Khelil ◽  
Ali Neji ◽  
Khaldoun Ben Hamda ◽  
Sabri Maaoui ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Binding Site ◽  
Candidate Genes ◽  
Brugada Syndrome ◽  
Genetic Variants ◽  
Sequence Variant ◽  
Α Subunit ◽  
Coding Sequence ◽  
Cardiac Sodium Channel ◽  
Scn5a Gene

AbstractBrugada syndrome (BrS) is a rare inherited cardiac arrhythmia associated with a high risk of sudden cardiac death (SCD) due to ventricular fibrillation (VF). BrS is characterized by coved-type ST-segment elevation in the right precordial leads (V1-V3) in the absence of structural heart disease. This pattern is spontaneous, or is unmasked by intravenous administration of Class I antiarrhythmic drugs. The SCN5A-encoded α-subunit of the NaV1.5 cardiac sodium channel has been linked to BrS, and mutations in SCN5A are identified in 15–30% of BrS cases. Genetic testing of BrS patients generally involves sequencing of protein-coding portions and flanking intronic regions of SCN5A, according to recent international guidelines. This excludes the regulatory untranslated regions (5’UTR and 3’UTR) from the routine genetic testing of BrS patients. We here screened the coding sequence, the flanking intronic regions as well as the 5’ and 3’UTR regions of SCN5A gene and further five candidate genes (GPD1L, SCN1B, KCNE3, SCN4B, and MOG1) in a Tunisian family diagnosed with Brugada syndrome.A new Q1000K mutation was identified on the SCN5A gene along with two common polymorphisms (H558R and D1819). Furthermore, multiple genetic variants were identified on the SCN5A 3’UTR, one of which is predicted to create additional microRNA (miRNAs) binding site for miR-1270. Additionally, we identified the hsa-miR-219a rs107822. No relevant coding sequence variant was identified in the remaining studied candidate genes. Although Q1000K is localized in the conserved binding site of MOG1 which predicts a functional consequence, this new mutation along with the additional variants were differentially distributed among the family members without any clear genotype-phenotype concordance. This gives extra evidences about the complexity of the disease and suggests that the occurrence and prognosis of BrS is most likely controlled by a combination of multiple genetic factors and exposures, rather than a single polymorphism/mutation. Most SCN5A polymorphisms were localized in non-coding regions hypothesizing an impact on the miRNA-target complementarities. In this regard, over-expression of miR-1270 led to a significant decrease of luciferase activity suggesting a direct role regulating SCN5A. Therefore, genetic variants that disrupt its binding affinity to SCN5A 3’UTR and/or its expression might cause loss of normal repression control and be associated to BrS.

scholarly journals Four novel mutations in the ALPL gene in Chinese patients with odonto, childhood, and adult hypophosphatasia

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Lijun Xu ◽  
Qianqian Pang ◽  
Yan Jiang ◽  
Ou Wang ◽  
Mei Li ◽  
...  
Keyword(s):  
Serum Alkaline Phosphatase ◽  
Gene Mutations ◽  
Dominant Negative ◽  
Chinese Patients ◽  
Dominant Negative Effect ◽  
Healthy Controls ◽  
Missense Mutations ◽  
Genetic Characteristics ◽  
Chinese Families ◽  
Negative Effect

Hypophosphatasia (HPP) is a rare inherited disorder characterized by defective bone and/or dental mineralization, and decreased serum alkaline phosphatase (ALP) activity. ALPL, the only gene related with HPP, encodes tissue non-specific ALP (TNSALP). Few studies were carried out in ALPL gene mutations in the Chinese population with HPP. The purpose of the present study is to elucidate the clinical and genetic characteristics of HPP in five unrelated Chinese families and two sporadic patients. Ten clinically diagnosed HPP patients from five unrelated Chinese families and two sporadic patients and fifty healthy controls were genetically investigated. All 12 exons and exon–intron boundaries of the ALPL gene were amplified by PCR and directly sequenced. The laboratory and radiological investigations were conducted simultaneously in these HPP ten patients. A 3D model of the TNSALP was used to predict the dominant negative effect of identified missense mutations. Three odonto, three childhood, and four adult types of HPP were clinically diagnosed. Ten mutations were identified in five unrelated Chinese families and two sporadic patients, including eight missense mutations and two frameshift mutations. Of which, four were novel: one frameshift mutation (p.R138Pfsx45); three missense mutations (p.C201R, p.V459A, p.C497S). No identical mutations and any other new ALPL mutations were found in unrelated 50 healthy controls. Our study demonstrated that the ALPL gene mutations are responsible for HPP in these Chinese families. These findings will be useful for clinicians to improve understanding of this heritable bone disorder.

scholarly journals Clinical and mutational spectrum of 4 Chinese families with glutaric aciduria type 1

2019 ◽  
Author(s):  
Xiaorong Shi ◽  
Qiaoyan Shao ◽  
Aidong Zheng ◽  
Wenghuang Xie
Keyword(s):  
Mutational Analysis ◽  
Southern China ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Glutaric Aciduria Type ◽  
Chinese Patients ◽  
Type I ◽  
Glutaric Aciduria Type 1 ◽  
Glutaric Aciduria ◽  
Molecular Aspects

Abstract Background To investigate clinical presentation and molecular aspects of five patients suffered from glutaric aciduria type I (GA-I ), a rare neurometabolic disorder caused by glutaryl-CoA dehydrogenase deficiency due to GCDH gene mutations. Methods All five patients were diagnosed by elevated urinary glutaric acid and GCDH gene analysis. Low protein diet supplemented with special formula, GABA analog and L-carnitine were initialed following laboratory confirmation of diagnosis. The clinical and biochemical features were analyzed, and mutational analysis of GCDH was conducted using Sanger sequencing. Results Clinical manifestations of 5 patients varied from macrocephaly to severe encephalopathy, with notably different phenotype between siblings with the same mutations. Three members present complex heterozygous mutations, while two sisters present homozygous mutations. Among them, four mutations in GCDH were identified (c.1133C>T 、c.1244-2A>C 、c.339delT 、c.406G>T). Of these four mutations, c.1244- 2A>C was found in four patients and c.339delT and c.1133C>T has not yet been reported until now. Conclusions In 5 Chinese patients with GA1, two novel mutations of GCDH gene were identified, which may expand the mutation spectrum of GCDH gene. What we found confirm that there is no correlation between clinical phenotype and genotype in GA-I patients, and c.1244-2A>C may be mutation hotspot in Southern China.

scholarly journals Identifying Gene Mutations in Autosomal Recessive Cerebellar Ataxias and Extending the Mutational Spectrum in China

2021 ◽  
Author(s):  
Xueping Chen ◽  
Xiaoqin Yuan ◽  
Qian-Qian Wei ◽  
RuWei Ou ◽  
Bei Cao ◽  
...  
Keyword(s):  
Cerebellar Ataxia ◽  
Autosomal Recessive ◽  
Gene Mutations ◽  
Autosomal Recessive Inheritance ◽  
Chinese Patients ◽  
Missense Mutations ◽  
Genetic Characteristics ◽  
Targeted Next Generation Sequencing ◽  
Cerebellar Ataxias ◽  
Autosomal Recessive Cerebellar Ataxias

Abstract Background: Autosomal recessive cerebellar ataxias (ARCA) are heterogeneous, complex, disabling neurodegenerative diseases characterized by autosomal recessive inheritance and cerebellar ataxia. Numerous mutations are described in several populations. However, in China, few data are available concerning ARCA. In this study, we aimed to identify ARCA-associated ataxia by targeted next-generation sequencing or whole-exome sequencing in a Chinese cohort, trying to determine clinical and genetic characteristics of Chinese patients with ARCA.Results: We identified 15 different mutations in 7 unrelated patients, of which 12 were novel, including seven missense mutations, three frameshift mutations, two splicing mutations, two nonsense mutations, and one inframe deletion mutation. The most frequent gene was ATM (3 patients), followed by SACS (2 patients), SYNE1 (2 patients), and SETX (1 patient). Specifically, 1 patient harbored mutations in both ATM and SYNE1. The phenotype was mainly cerebellar ataxia in all these cases. However, peripheral neuropathy, dystonia, oculomotor abnormalities, pyramidal tract dysfunction, cognitive impairment, and epilepsy were also revealed. Patients who harbored different gene mutations showed mutational heterogeneity. Conclusions: Our results indicate that ARCA-associated gene mutations are uncommon with additional clinical features in the Chinese population, and advanced sequencing is required to aid the diagnosis of undetermined cerebellar ataxia in Chinese patients.

The Spectrum of SCN5A Gene Mutations in Spanish Brugada Syndrome Patients

2010 ◽  
Vol 63 (7) ◽  
pp. 856-859 ◽  
Author(s):  
Mónica García-Castro ◽  
Cristina García ◽  
Julián R. Reguero ◽  
Ana Miar ◽  
José M. Rubín ◽  
...  
Keyword(s):  
Brugada Syndrome ◽  
Gene Mutations ◽  
Scn5a Gene
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