scholarly journals The mining and construction of a knowledge base for gene-disease association in mitochondrial diseases

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wei Wang ◽  
Junying Song ◽  
Yunhai Chuai ◽  
Fu Chen ◽  
Chunlan Song ◽  
...  
Keyword(s):  
Knowledge Base ◽  
Nuclear Dna ◽  
Metabolic Diseases ◽  
Treatment Strategies ◽  
Gene Mutations ◽  
Mitochondrial Diseases ◽  
Disease Association ◽  
Database Integration ◽  
Gene Testing ◽  
Sequencing Method

AbstractMitochondrial diseases are a group of heterogeneous genetic metabolic diseases caused by mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) gene mutations. Mining the gene-disease association of mitochondrial diseases is helpful for understanding the pathogenesis of mitochondrial diseases, for carrying out early clinical diagnosis for related diseases, and for formulating better treatment strategies for mitochondrial diseases. This project researched the relationship between genes and mitochondrial diseases, combined the Malacards, Genecards, and MITOMAP disease databases to mine the knowledge on mitochondrial diseases and genes, used database integration and the sequencing method of the phenolyzer tool to integrate disease-related genes from different databases, and sorted the disease-related candidate genes. Finally, we screened 531 mitochondrial related diseases, extracted 26,723 genes directly or indirectly related to mitochondria, collected 24,602 variant sites on 1474 genes, and established a mitochondrial disease knowledge base (MitDisease) with a core of genes, diseases, and variants. This knowledge base is helpful for clinicians who want to combine the results of gene testing for diagnosis, to understand the occurrence and development of mitochondrial diseases, and to develop corresponding treatment methods.

scholarly journals Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)—A Condition Associated with Heightened Sympathetic Activation

2021 ◽  
Vol 22 (8) ◽  
pp. 4241
Author(s):  
Revathy Carnagarin ◽  
Kearney Tan ◽  
Leon Adams ◽  
Vance B. Matthews ◽  
Marcio G. Kiuchi ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Treatment Strategies ◽  
Adverse Outcomes ◽  
Metabolic Dysfunction ◽  
Sympathetic Activation ◽  
Beneficial Effects ◽  
Adverse Health Outcomes

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common liver disease affecting a quarter of the global population and is often associated with adverse health outcomes. The increasing prevalence of MAFLD occurs in parallel to that of metabolic syndrome (MetS), which in fact plays a major role in driving the perturbations of cardiometabolic homeostasis. However, the mechanisms underpinning the pathogenesis of MAFLD are incompletely understood. Compelling evidence from animal and human studies suggest that heightened activation of the sympathetic nervous system is a key contributor to the development of MAFLD. Indeed, common treatment strategies for metabolic diseases such as diet and exercise to induce weight loss have been shown to exert their beneficial effects at least in part through the associated sympathetic inhibition. Furthermore, pharmacological and device-based approaches to reduce sympathetic activation have been demonstrated to improve the metabolic alterations frequently present in patients with obesity, MetSand diabetes. Currently available evidence, while still limited, suggests that sympathetic activation is of specific relevance in the pathogenesis of MAFLD and consequentially may offer an attractive therapeutic target to attenuate the adverse outcomes associated with MAFLD.

scholarly journals Treatment for mitochondrial diseases

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Tongling Liufu ◽  
Zhaoxia Wang
Keyword(s):  
Clinical Trials ◽  
Nuclear Dna ◽  
Mitochondrial Diseases ◽  
Cochrane Collaboration ◽  
Potential Bias ◽  
Leber Hereditary Optic Neuropathy ◽  
Pharmacological Agents ◽  
Unpublished Studies ◽  
New Treatment ◽  
Allotopic Expression

AbstractMitochondrial diseases are predominantly caused by mutations of mitochondrial or nuclear DNA, resulting in multisystem defects. Current treatments are largely supportive, and the disorders progress relentlessly. Nutritional supplements, pharmacological agents and physical therapies have been used in different clinical trials, but the efficacy of these interventions need to be further evaluated. Several recent reviews discussed some of the interventions but ignored bias in those trials. This review was conducted to discover new studies and grade the original studies for potential bias with revised Cochrane Collaboration guidelines. We focused on seven published studies and three unpublished studies; eight of these studies showed improvement in outcome measurements. In particular, two of the interventions have been tested in studies with strict design, which we believe deserve further clinical trials with a large sample. Additionally, allotopic expression of the ND4 subunit seemed to be an effective new treatment for patients with Leber hereditary optic neuropathy.

The effect of a lollipop on vocally disruptive behavior in a patient with frontotemporal dementia: a case-study

2014 ◽  
Vol 26 (12) ◽  
pp. 2023-2026 ◽  
Author(s):  
W. F. Fick ◽  
J. P. van der Borgh ◽  
S. Jansen ◽  
R. T. C. M. Koopmans
Keyword(s):  
Beneficial Effect ◽  
Knowledge Base ◽  
Frontotemporal Dementia ◽  
Disruptive Behavior ◽  
Treatment Strategies ◽  
Limited Knowledge ◽  
People With Dementia

ABSTRACTA problematic and disturbing behavior which can develop in people with dementia, is vocally disruptive behavior (VDB). To date, the study of VDB is underdeveloped and with only a limited knowledge base. Medications commonly used in VDB have limited benefits and specific risks in patients with dementia. This report details the case of a patient with frontotemporal dementia with VDB, which responded very well by providing a lollipop. Subsequently, we pose theory-based hypotheses in order to try to explain the beneficial effect of this intervention. This may contribute to a better understanding of VDB and possible treatment strategies.

scholarly journals Mitochondrial DNA Replacement Techniques to Prevent Human Mitochondrial Diseases

2021 ◽  
Vol 22 (2) ◽  
pp. 551
Author(s):  
Luis Sendra ◽  
Alfredo García-Mares ◽  
María José Herrero ◽  
Salvador F. Aliño
Keyword(s):  
Mitochondrial Dna ◽  
Nuclear Dna ◽  
Genetic Disorders ◽  
Mitochondrial Diseases ◽  
Legal Regulation ◽  
Donor Oocyte ◽  
Legal Position ◽  
Ethical And Legal Issues ◽  
Mitochondrial Replacement Techniques ◽  
Do So

Background: Mitochondrial DNA (mtDNA) diseases are a group of maternally inherited genetic disorders caused by a lack of energy production. Currently, mtDNA diseases have a poor prognosis and no known cure. The chance to have unaffected offspring with a genetic link is important for the affected families, and mitochondrial replacement techniques (MRTs) allow them to do so. MRTs consist of transferring the nuclear DNA from an oocyte with pathogenic mtDNA to an enucleated donor oocyte without pathogenic mtDNA. This paper aims to determine the efficacy, associated risks, and main ethical and legal issues related to MRTs. Methods: A bibliographic review was performed on the MEDLINE and Web of Science databases, along with searches for related clinical trials and news. Results: A total of 48 publications were included for review. Five MRT procedures were identified and their efficacy was compared. Three main risks associated with MRTs were discussed, and the ethical views and legal position of MRTs were reviewed. Conclusions: MRTs are an effective approach to minimizing the risk of transmitting mtDNA diseases, but they do not remove it entirely. Global legal regulation of MRTs is required.

Novel Recurrent Altered Genes in Chinese Patients With Anaplastic Thyroid Cancer

2021 ◽  
Author(s):  
Lingyun Zhang ◽  
Zhixiang Ren ◽  
Zhengzheng Su ◽  
Yang Liu ◽  
Tian Yang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Copy Number ◽  
Treatment Strategies ◽  
Gene Mutations ◽  
Anaplastic Thyroid Cancer ◽  
Chinese Patients ◽  
Driver Gene ◽  
Phosphatidylinositol 3 Kinase ◽  
Entire Cohort ◽  
Whole Exome

Abstract Background Anaplastic thyroid cancer (ATC) is a rare but lethal malignancy, and few systematic investigations on genomic profiles of ATC have been performed in Chinese patients. Methods Fifty-four ATC patients in West China Hospital between 2010 to 2020 were retrospectively analyzed, while 29 patients with available samples were sequenced by whole-exome sequencing (WES). The associations between genomic alterations and clinical characteristics were statistically evaluated. Results The median overall survival was 3.0 months in the entire cohort, which was impacted by multiple clinical features, including age, tumor size, and different treatment strategies. In the WES cohort, totally 797 nonsilent mutations were detected; the most frequently altered genes were TP53 (48%), BRAF (24%), PIK3CA (24%), and TERT promoter (21%). Although these mutations have been well-reported in previous studies, ethnic specificity was exhibited in terms of mutation frequency. Moreover, several novel significantly mutated genes were identified including RBM15 (17%), NOTCH2NL (14%), CTNNA3 (10%), and KATNAL2 (10%). WES-based copy number alteration analysis also revealed a high frequent gain of NOTCH2NL (41%), which induced its increased expression. Gene mutations and copy number alterations were enriched in phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin (mTOR), NOTCH, and WNT pathways. Conclusions This study reveals shared and ethnicity-specific genomic profiles of ATC in Chinese patients and suggests NOTCH2NL may act as a novel candidate driver gene for ATC tumorigenesis.

scholarly journals Understanding mitochondrial myopathies: a review

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4790 ◽  
Author(s):  
Abhimanyu S. Ahuja
Keyword(s):  
Speech Therapy ◽  
Nuclear Dna ◽  
Severe Disease ◽  
Mitochondrial Diseases ◽  
The Body ◽  
Genetic Mutations ◽  
Mitochondrial Myopathies ◽  
Positive Side ◽  
Organ Systems ◽  
New Research

Mitochondria are small, energy-producing structures vital to the energy needs of the body. Genetic mutations cause mitochondria to fail to produce the energy needed by cells and organs which can cause severe disease and death. These genetic mutations are likely to be in the mitochondrial DNA (mtDNA), or possibly in the nuclear DNA (nDNA). The goal of this review is to assess the current understanding of mitochondrial diseases. This review focuses on the pathology, causes, risk factors, symptoms, prevalence data, symptomatic treatments, and new research aimed at possible preventions and/or treatments of mitochondrial diseases. Mitochondrial myopathies are mitochondrial diseases that cause prominent muscular symptoms such as muscle weakness and usually present with a multitude of symptoms and can affect virtually all organ systems. There is no cure for these diseases as of today. Treatment is generally supportive and emphasizes symptom management. Mitochondrial diseases occur infrequently and hence research funding levels tend to be low in comparison with more common diseases. On the positive side, quite a few genetic defects responsible for mitochondrial diseases have been identified, which are in turn being used to investigate potential treatments. Speech therapy, physical therapy, and respiratory therapy have been used in mitochondrial diseases with variable results. These therapies are not curative and at best help with maintaining a patient’s current abilities to move and function.

scholarly journals Characteristics of the mutation spectrum identified by comprehensive investigation of the CFTR gene in the Russian patients

2019 ◽  
Vol 47 (1) ◽  
pp. 38-46
Author(s):  
N. V. Petrova ◽  
A. Yu. Marakhonov ◽  
T. A. Vasilyeva ◽  
N. Yu. Kashirskaya ◽  
E. I. Kondratyeva ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Hereditary Disease ◽  
Mutation Spectrum ◽  
Missense Mutations ◽  
Nonsense Mutations ◽  
Sequencing Method ◽  
Novel Variants ◽  
Frequent Mutations ◽  
Large Rearrangements

Rationale: Cystic fibrosis (CF; OMIM 219700) is a  common hereditary disease caused by mutations in the CFTR gene (OMIM 602421). The distribution and frequencies of the CFTR gene mutations vary considerably between countries and ethnic groups. By now about 11%  alleles of the CFTR gene remain unidentified after testing for frequent mutations in the Russian patients. A full determination of the mutation spectrum in the CFTR gene is necessary to optimize medical and genetic assistance to the population and to implement the achievements of targeted therapy in the treatment of CF patients.Materials and methods: The sample included 121 Russian CF patients, in whom testing for 34 routinely analyzed mutations did not identify one (n = 107) or both (n = 14) mutant alleles. Assessment of the coding sequence of the CFTR gene, including the regions of exon-intron junctions, 5’- and 3’-untranslated regions was performed by the Sanger sequencing method; in addition, the search for large rearrangements was conducted by the multiplex ligation-dependent probe amplification (MLPA) method.Results: In addition to the previously identified, 88  more variants were determined, including 28  missense mutations, 15  nonsense mutations, 18 frameshift mutations (14 deletions, 4  insertions), 14  splicing mutations, 1  in-frame insertion, 1  in-frame deletion, 1  in/del mutation, and 10  large rearrangements (7  deletions, 3  duplications). Twenty three (23) novel variants were sequenced. Four (4) complex mutant alleles were found. Sixty (60) variants are found once each. One hundred and thirty four (134) of 135 tested mutant alleles were identified.Conclusion: Consequent use of the sequencing and MLPA methods has allowed for identification of a high proportion of the tested mutant alleles in CF patients from Russia (134/135, > 99%), to detect a  significant diversity of the CFTR mutation spectrum (88  additional variants, 32  of them novel), a  number of repeated mutations (c.2353C>T, c.1240_1244delCAAAA, c.1766+1G>A and c.3929G>A) encountered in 5 or more unrelated patients, which could be included in the panel of routinely analyzed variants in the Russian CF patients; and a high proportion of large rearrangements of the CFTR gene. 

The heart in neuromuscular disease: primary mitochondrial diseases

ESC CardioMed ◽  
2018 ◽  
pp. 1528-1530
Author(s):  
Denis Duboc
Keyword(s):  
Neuromuscular Disease ◽  
Nuclear Dna ◽  
Single Cells ◽  
Mitochondrial Diseases ◽  
Respiratory Chain Complexes ◽  
Base Pairs ◽  
Daughter Cells ◽  
Dna Molecule ◽  
Chain Complexes ◽  
Genes Encoding

Mitochondria are responsible for energy production in most eukaryotic cells. Each cell contains at least one mitochondrion and every mitochondrion contains two to ten copies of a circular DNA molecule (mitochondrial DNA or mtDNA). Cardiomyocytes contain approximately 10,000 mtDNA copies. MtDNA is composed of around 16,500 base pairs and 37 genes encoding 13 subunits of the respiratory chain complexes I, III, IV, and V, 22 mitochondrial tRNAs and 2 rRNAs. With each cell division, mitochondria and mtDNA are randomly distributed to daughter cells. In humans, mitochondria are inherited exclusively from the mother. In healthy people mtDNA copies are usually identical at birth (homoplasmy) but with ageing, mtDNA is particularly prone to somatic mutation because, unlike nuclear DNA, it is continuously replicated, even in non-dividing tissues such as myocardium. This can lead to the propagation of somatic mutations within single cells by a process called clonal expansion. In addition, mtDNA lacks an extensive DNA repair mechanism.

scholarly journals Proximal Myopathy due to m.5835G>A Mutation in Mitochondrial MT-TY Gene

2018 ◽  
Vol 2018 ◽  
pp. 1-4 ◽  
Author(s):  
C. Simoncini ◽  
V. Montano ◽  
G. Alì ◽  
R. Costa ◽  
G. Siciliano ◽  
...  
Keyword(s):  
Clinical Phenotype ◽  
Gene Mutations ◽  
Mitochondrial Diseases ◽  
Leigh Syndrome ◽  
Phenotype Correlation ◽  
Mitochondrial Trna ◽  
Gene Coding ◽  
Clinical Presentations ◽  
Wide Range ◽  
Proximal Myopathy

Mitochondrial (mt) tRNA (MTT) gene mutations are an important cause of mitochondrial diseases and are associated with a wide range of clinical presentations. Most mutations fall into three mitochondrial tRNAs (tRNAIle, tRNALeu (UUR), and tRNALys) and are responsible for half of the mitochondrial diseasees associated with tRNA mutation, with MERRF, MELAS, mitochondrial myopathy, and Leigh syndrome being the most frequent phenotypes. More than 100 tRNA pathogenetic mutations are described, showing little correlation between the observed clinical phenotype and a specific mitochondrial tRNA mutation. Furthermore different mutation can manifest with similar clinical phenotypes, making the genotype-phenotype correlation difficult. Here we report the case of an Italian 53-year-old woman presenting with a proximal myopathy and the m.5835G>A mutation in MT-TY gene coding for the mitochondrial tRNA Tyrosine gene.

scholarly journals Detected EGFR mutation in cerebrospinal fluid of lung adenocarcinoma patients with meningeal metastasis

Open Medicine ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. 93-96 ◽  
Author(s):  
Jiang Rong ◽  
Ma Chunhua ◽  
Lv Yuan ◽  
Mu Ning ◽  
Li Jinduo ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Lung Adenocarcinoma ◽  
Gene Mutation ◽  
Direct Sequencing ◽  
Gene Mutations ◽  
Egfr Mutations ◽  
Egfr Gene ◽  
Sequencing Method ◽  
Direct Sequencing Method ◽  
Egfr Gene Mutation

AbstractObjectiveTo discuss the application of ARMS method to detect EGFR gene mutation in cerebrospinal fluid of lung adenocarcinoma patients with meningeal metastasis.Methods5 cases of lung adenocarcinoma were identified with meningeal metastasis that were cleared EGFR gene mutation by gene sequencing method. From each patient 5ml cerebrospinal fluid was obtained by lumbar puncture. ARMS method was used to detect EGFR mutations in cerebrospinal fluid.Results5 samples of cerebrospinal fluid were successfully detected by ARMS method, 3 samples found that EGFR gene mutations, the mutations in line with direct sequencing method.ConclusionARMS method can be used to detect EGFR gene mutations of cerebrospinal fluid samples in lung adenocarcinoma with meningeal metastasis. But cerebrospinal fluid specimens from histological specimens, blood samples need to be confirmed by further comparative study whether there is advantage.

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