Journal articles on the topic 'Genetic disorders Pathophysiology'
To see the other types of publications on this topic, follow the link: Genetic disorders Pathophysiology.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Genetic disorders Pathophysiology.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Gyorfi, Michael, Adam Rupp, and Alaa Abd-Elsayed. "Fibromyalgia Pathophysiology." Biomedicines 10, no. 12 (November 29, 2022): 3070. http://dx.doi.org/10.3390/biomedicines10123070.
Full textAbstract:
This article examines the biological, genetic, and environmental aspects of fibromyalgia that may have an impact on its pathogenesis. Symptoms of fibromyalgia may be related to aberrations in the endogenous inhibition of pain as well as changes in the central processing of sensory input. Genetic research has revealed familial aggregation of fibromyalgia and other related disorders like major depressive disorder. Dysfunctional pain processing may also be influenced by exposure to physical or psychological stressors, abnormal biologic reactions in the autonomic nervous system, and neuroendocrine responses. With more research the pathophysiology of fibromyalgia will be better understood, leading to more logical and focused treatment options for fibromyalgia patients.
2
Charoenngam, Nipith, Aryan Nasr, Arash Shirvani, and Michael F. Holick. "Hereditary Metabolic Bone Diseases: A Review of Pathogenesis, Diagnosis and Management." Genes 13, no. 10 (October 17, 2022): 1880. http://dx.doi.org/10.3390/genes13101880.
Full textAbstract:
Hereditary metabolic bone diseases are characterized by genetic abnormalities in skeletal homeostasis and encompass one of the most diverse groups among rare diseases. In this review, we examine 25 selected hereditary metabolic bone diseases and recognized genetic variations of 78 genes that represent each of the three groups, including sclerosing bone disorders, disorders of defective bone mineralization and disorder of bone matrix and cartilage formation. We also review pathophysiology, manifestation and treatment for each disease. Advances in molecular genetics and basic sciences has led to accurate genetic diagnosis and novel effective therapeutic strategies for some diseases. For other diseases, the genetic basis and pathophysiology remain unclear. Further researches are therefore crucial to innovate ways to overcome diagnostic challenges and develop effective treatment options for these orphan diseases.
3
Himmerich, Hubertus, Jessica Bentley, Carol Kan, and Janet Treasure. "Genetic risk factors for eating disorders: an update and insights into pathophysiology." Therapeutic Advances in Psychopharmacology 9 (January 2019): 204512531881473. http://dx.doi.org/10.1177/2045125318814734.
Full textAbstract:
Genome-wide-association studies (GWASs), epigenetic, gene-expression and gene–gene interaction projects, nutritional genomics and investigations of the gut microbiota have increased our knowledge of the pathophysiology of eating disorders (EDs). However, compared with anorexia nervosa, genetic studies in patients with bulimia nervosa and binge-eating disorder are relatively scarce, with the exception of a few formal genetic and small-sized candidate–gene-association studies. In this article, we review important findings derived from formal and molecular genetics in order to outline a genetics-based pathophysiological model of EDs. This model takes into account environmental and nutritional factors, genetic factors related to the microbiome, the metabolic and endocrine system, the immune system, and the brain, in addition to phenotypical traits of EDs. Shortcomings and advantages of genetic research in EDs are discussed against the historical background, but also in light of potential future treatment options for patients with EDs.
4
Wandile, Pranali. "Fibromyalgia Management with Homeopathy." Homœopathic Links 30, no. 04 (December 2017): 245–49. http://dx.doi.org/10.1055/s-0037-1608614.
Full textAbstract:
AbstractFibromyalgia is one of the most common genetically inherited chronic affective spectrum disorders (ASD). Other ASD disorders are psychiatric and medical conditions such as irritable bowel syndrome (IBS), migraine, cataplexy—attention-deficit/hyperactivity disorder, bulimia nervosa, dysthymic disorder, generalised anxiety disorder, major depressive disorder (MDD), obsessive-compulsive disorder, panic disorder, posttraumatic stress disorder, premenstrual dysphoric disorder, rheumatoid arthritis, and social phobia. Apart from genetic factors, neuroendocrine, autonomic nervous system abnormalities, psychosocial variables and environmental stressors contribute in the pathophysiology of fibromyalgia and other associated disorders. In this article, we reviewed etiology, pathophysiology, maintaining and triggering factors, and various treatment options for fibromyalgia. Apart from the pain management, this condition can be managed by ancillary method of treatment. However, due to the genetic cause of the disease, there is very little to offer for its complete cure. Homeopathic miasmatic treatment focuses on the genetic cause of the disease for its complete annihilation while also providing various acute remedies for the temporary pain management. We reviewed homeopathy treatment management and various remedies, which have much to offer for this chronic condition while considering its genetic, triggering and maintaining factors.
5
Gavryutina, Irina, Lawrence Fordjour, and Vivian L. Chin. "Genetics of Thyroid Disorders." Endocrines 3, no. 2 (April 13, 2022): 198–213. http://dx.doi.org/10.3390/endocrines3020018.
Full textAbstract:
Thyroid diseases in children and adolescents include acquired or congenital conditions, including genetic disorders either isolated or part of a syndrome. Briefly, we will review the physiology and pathophysiology of the thyroid gland and its disorders. The aim of this chapter is to describe genetic abnormalities of the thyroid gland.
6
Clerici, Mario, Beatrice Arosio, Emanuela Mundo, Elisabetta Cattaneo, Sara Pozzoli, Bernardo Dell'Osso, Carlo Vergani, Daria Trabattoni, and A. Carlo Altamura. "Cytokine Polymorphisms in the Pathophysiology of Mood Disorders." CNS Spectrums 14, no. 8 (August 2009): 419–25. http://dx.doi.org/10.1017/s1092852900020393.
Full textAbstract:
ABSTRACTIntroduction: An increasing amount of data suggests that dysregulation of the immune system, including the cytokine network, is associated with the etiology and pathophysiology of mood disorders. Genes encoding cytokines are highly polymorphic and single nucleotide polymorphisms, associated with increased or reduced cytokine production, have been described. The aim of this study was to define the genetic immunologic scenario associated with major depressive disorder (MDD) and bipolar disorder.Methods: Eighty-four Italian outpatients affected by bipolar disorder type I, bipolar disorder type II, or MDD, and 363 healthy controls were enrolled into the study. We analyzed allele and genotype distribution of −308 (G/A) tumor necrosis factor-α (TNF-α), +874 (T/A) interferon-γ (IFN-γ), -174 (G/C) interleukin (IL)-6, and −1082 (G/A) IL-10 promoter polymorphisms by Polymerase Chain Reaction Sequence Specific Primers technique.Results: We observed different genotype and allele distributions of TNF-α, IFN-γ, and IL-10 polymorphisms in the three groups of patients analyzed. In particular, bipolar II patients were characterized by an absence of adenine (A) high producer allele of TNF-α (P<.001) and a lower percentage of TT high producer genotype of IFN-γ (P <.001); bipolar I individuals showed reduced percentage of AA low producer genotype of IL-10 (P<.001). Both bipolar I and bipolar II patients not carrying guanine (G) high producer IL-6 allele showed a lower mean age at onset (P=.048).Conclusion: These data support the existence of a genetic profile related to pro-inflammatory cytokines in patients affected by mood disorders. The differences observed across the three clinical phenotypes suggest the presence of different pathogenetic mechanisms involved in the susceptibility of phenotypically different mood disorders.
7
Miller, Assia, Serina Mathew, Sneha Patel, Lawrence Fordjour, and Vivian L. Chin. "Genetic Disorders of Calcium and Phosphorus Metabolism." Endocrines 3, no. 1 (March 17, 2022): 150–67. http://dx.doi.org/10.3390/endocrines3010014.
Full textAbstract:
In this review, we describe genetic mutations affecting metabolic pathways of calcium and phosphorus homeostasis. Calcium and phosphorus homeostasis has tight hormonal regulation by three major hormones: vitamin D, parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23). We describe the physiology and pathophysiology of disorders, their biochemical profile, clinical characteristics, diagnostics, and treatments.
8
Keir, Holly R., and James D. Chalmers. "Pathophysiology of Bronchiectasis." Seminars in Respiratory and Critical Care Medicine 42, no. 04 (July 14, 2021): 499–512. http://dx.doi.org/10.1055/s-0041-1730891.
Full textAbstract:
AbstractBronchiectasis is a complex, heterogeneous disorder defined by both a radiological abnormality of permanent bronchial dilatation and a clinical syndrome. There are multiple underlying causes including severe infections, mycobacterial disease, autoimmune conditions, hypersensitivity disorders, and genetic conditions. The pathophysiology of disease is understood in terms of interdependent concepts of chronic infection, inflammation, impaired mucociliary clearance, and structural lung damage. Neutrophilic inflammation is characteristic of the disease, with elevated levels of harmful proteases such as neutrophil elastase associated with worse outcomes. Recent data show that neutrophil extracellular trap formation may be the key mechanism leading to protease release and severe bronchiectasis. Despite the dominant of neutrophilic disease, eosinophilic subtypes are recognized and may require specific treatments. Neutrophilic inflammation is associated with elevated bacterial loads and chronic infection with organisms such as Pseudomonas aeruginosa. Loss of diversity of the normal lung microbiota and dominance of proteobacteria such as Pseudomonas and Haemophilus are features of severe bronchiectasis and link to poor outcomes. Ciliary dysfunction is also a key feature, exemplified by the rare genetic syndrome of primary ciliary dyskinesia. Mucus symptoms arise through goblet cell hyperplasia and metaplasia and reduced ciliary function through dyskinesia and loss of ciliated cells. The contribution of chronic inflammation, infection, and mucus obstruction leads to progressive structural lung damage. The heterogeneity of the disease is the most challenging aspect of management. An understanding of the pathophysiology of disease and their biomarkers can help to guide personalized medicine approaches utilizing the concept of “treatable traits.”
9
Musambil, Mohthash, Khalid Al-Rubeaan, Sara Al-Qasim, Dhekra Al Naqeb, and Abdulrahman Al-Soghayer. "Primary Hypertriglyceridemia: A Look Back on the Clinical Classification and Genetics of the Disease." Current Diabetes Reviews 16, no. 6 (June 14, 2020): 521–31. http://dx.doi.org/10.2174/1573399815666190502164131.
Full textAbstract:
Introduction: Hypertriglyceridemia (HTG) is one of the most common metabolic disorders leading to pancreatitis and cardiovascular disease. HTG develops mostly due to impaired metabolism of triglyceride-rich lipoproteins. Although monogenic types of HTG exist, most reported cases are polygenic in nature. Aim: This review article is focused on the classification of Primary HTG and the genetic factors behind its development with the aim of providing clinicians a useful tool for early detection of the disease in order to administer proper and effective treatment. Discussion: HTG is often characterized by a complex phenotype resulting from interactions between genetic and environmental factors. In many instances, the complexity, perplexing causes, and classification of HTG make it difficult for clinicians to properly diagnose and manage the disorder. Better availability of information on its pathophysiology, genetic factors involved, environmental causes, and their interactions could help in understanding such complex disorders and could support its effective diagnosis and treatment. Conclusion: The current review has summarized the case definition, epidemiology, pathophysiology, clinical presentation, classification, associated genetic factors, and scope of genetic screening in the diagnosis of primary HTG.
10
Yadav, Monu, Ishu Sardana, Amarjeet Sharma, Nidhi Sharma, Kalpana Nagpal, and Paramjeet Malik. "Emerging Pathophysiological Targets of Psoriasis for Future Therapeutic Strategies." Infectious Disorders - Drug Targets 20, no. 4 (October 16, 2020): 409–22. http://dx.doi.org/10.2174/1871526519666190617162701.
Full textAbstract:
Psoriasis is a chronic autoimmune skin disorder which involves complex interactions between genes, keratinocytes, T-cells and inflammatory cells. It affects 2-3% population worldwide. Molecular biology and cellular immunology of psoriasis, when linked with biotechnology and genetic studies can help researchers to understand the pathophysiology of psoriasis. T-cells activation, keratinocyte hyperproliferation, and angiogenesis are the core mechanisms entailed in the development of psoriasis lesion. Investigators are trying to overcome the challenges of complex pathophysiology pathways involved in this disorder. The different possible hypotheses for its pathophysiology such as growth factors, enzymes, inflammation, and genetic factors mediated pathophysiology have been described in the present review paper in detail. Clinically available drugs only control the symptoms of psoriasis but are not effective for the treatment of the disorder completely and are also associated with some side effects such as itching, renal disorders, hematologic, nonmelanoma skin cancer, pulmonary, gastrointestinal toxicity, etc. This paper made an effort to understand the pathophysiological targets, discuss the research done so far and the treatments available for the effective management of psoriasis.
11
Olmez, Akgun, and Haluk Topaloglu. "Hereditary spastic paraplegia:Pathogenesis and pathophysiology." NATIONAL JOURNAL OF NEUROLOGY, no. 5 (December 4, 2018): 1–13. http://dx.doi.org/10.28942/nnj.v1i5.105.
Full textAbstract:
Hereditary spastic paraplegias constitute a larger group of disorders than expected.
Autosomal dominant types are mainly composed of SPAST, Atlastin (SPG3A) and REEP1 Genetic testing is suggested mainly for these genes.
The most common autosomal recessive type is SPG11, hereditary spastic paraplegia with thin corpus callosum, but SPG15 shares the same clinical features with SPG11. Genetic testing should be done for both if thin corpus callosum is present in patients.
How different genes with many different biological functions, including axonal transport, mitochondrial functions, fatty acid and cholesterol pathways and DNA repair defects, cause hereditary spastic paraplegia is still unknown.
12
Hsu, Chia-Jui, Lee-Chin Wong, and Wang-Tso Lee. "Immunological Dysfunction in Tourette Syndrome and Related Disorders." International Journal of Molecular Sciences 22, no. 2 (January 16, 2021): 853. http://dx.doi.org/10.3390/ijms22020853.
Full textAbstract:
Chronic tic disorder and Tourette syndrome are common childhood-onset neurological diseases. However, the pathophysiology underlying these disorders is unclear, and most studies have focused on the disinhibition of the corticostriatal–thalamocortical circuit. An autoimmune dysfunction has been proposed in the pathogenetic mechanism of Tourette syndrome and related neuropsychiatric disorders such as obsessive–compulsive disorder, autism, and attention-deficit/hyperactivity disorder. This is based on evidence from animal model studies and clinical findings. Herein, we review and give an update on the clinical characteristics, clinical evidence, and genetic studies in vitro as well as animal studies regarding immune dysfunction in Tourette syndrome.
13
Teoh, Hooi Ling, Kate Carey, Hugo Sampaio, David Mowat, Tony Roscioli, and Michelle Farrar. "Inherited Paediatric Motor Neuron Disorders: Beyond Spinal Muscular Atrophy." Neural Plasticity 2017 (2017): 1–22. http://dx.doi.org/10.1155/2017/6509493.
Full textAbstract:
Paediatric motor neuron diseases encompass a group of neurodegenerative diseases characterised by the onset of muscle weakness and atrophy before the age of 18 years, attributable to motor neuron loss across various neuronal networks in the brain and spinal cord. While the genetic underpinnings are diverse, advances in next generation sequencing have transformed diagnostic paradigms. This has reinforced the clinical phenotyping and molecular genetic expertise required to navigate the complexities of such diagnoses. In turn, improved genetic technology and subsequent gene identification have enabled further insights into the mechanisms of motor neuron degeneration and how these diseases form part of a neurodegenerative disorder spectrum. Common pathophysiologies include abnormalities in axonal architecture and function, RNA processing, and protein quality control. This review incorporates an overview of the clinical manifestations, genetics, and pathophysiology of inherited paediatric motor neuron disorders beyond classic SMN1-related spinal muscular atrophy and describes recent advances in next generation sequencing and its clinical application. Specific disease-modifying treatment is becoming a clinical reality in some disorders of the motor neuron highlighting the importance of a timely and specific diagnosis.
14
Chung, Brian K., and Tom H. Karlsen. "Genetic Discoveries Highlight Environmental Factors as Key Drivers of Liver Disease." Digestive Diseases 35, no. 4 (2017): 323–33. http://dx.doi.org/10.1159/000456583.
Full textAbstract:
Background: Over the last 50 years, genetic studies have uncovered a spectrum of rare and common alleles that confer susceptibility to both Mendelian and complex forms of liver disease. For disorders of Mendelian inheritance, identification of the causal variants has demonstrated that common environmental exposures can elicit severe liver pathogenesis in predisposed individuals. Specific environmental triggers for complex liver disorders are largely unknown; however, large-scale association studies indicate that environmental triggers are the predominant factors in driving liver pathophysiology. Key Messages: In Mendelian liver disorders, a single rare variant of major effect is often responsible for disease development. Gene-sequencing technologies have greatly facilitated the discovery of causal variants for Mendelian diseases and are increasingly utilized in molecular and clinical genetics for diagnostic and counselling purposes. By contrast, genetic susceptibility for complex liver disorders is heterogeneous, as many different genes acting on multiple distinct pathways influence disease onset and severity. Risk variants for complex liver disorders are relatively common, typically of small effect size and detected by genome-wide association studies (GWAS), which compare the genetic variation of specific loci using thousands of patients and healthy controls. Thus far, GWAS have detected dozens of unique and overlapping risk alleles for complex liver disease, but these account for less than a quarter of the overall disease liability. These observations emphasize that environmental exposures on a background of genetic predisposition are significant drivers of liver pathophysiology. Rare variants of large effect size, undetectable by GWAS, may also affect the development of complex disease on a case-to-case basis but evidence for such a scenario remains to be determined. Conclusions: Genetic technologies have identified numerous risk genes for Mendelian and complex liver disorders transforming disease recognition. For complex liver disorders, deciphering the interplay between genetic risk and environment determinants remains a significant challenge for unlocking the development of novel and personalized interventions.
15
Balint, Bettina, Angela Vincent, Hans-Michael Meinck, Sarosh R. Irani, and Kailash P. Bhatia. "Movement disorders with neuronal antibodies: syndromic approach, genetic parallels and pathophysiology." Brain 141, no. 1 (September 25, 2017): 13–36. http://dx.doi.org/10.1093/brain/awx189.
Full text
16
Hollander, E., and J. Rosen. "Impulsivity." Journal of Psychopharmacology 14, no. 2_suppl1 (March 2000): S39—S44. http://dx.doi.org/10.1177/02698811000142s106.
Full textAbstract:
Disorders characterized by impulsivity include disorders of impulse control (intermittent explosive disorder, pyromania, kleptomania, pathological gambling and trichotillomania), paraphilias, sexual impulsions and sexual addictions and impulsive aggression personality disorders (borderline, antisocial, histrionic and narcissistic personality disorders). Impulsivity has a substantial impact on both individuals and society. Impulse control disorders may be conceptualized as a subset of the obsessive-compulsive spectrum. In this article, we examine the genetic and neurobiological aetiology of these disorders and possible treatment options. The link between serotonergic dysfunction and the pathophysiology of impulsivity is discussed, and studies that examine the efficacy of various selective serotonin reuptake inhibitors and other alternatives in the treatment of impulsive disorders such as pathological gambling, sexual addictions and borderline personality disorder are presented.
17
Khan, Muhammad Qasim, and Syeda Marriam Bakhtiar. "Prospects of Single Cell Omics (SCO) Analysis for Investigating Nervous System Disorders." Current Trends in OMICS 2, no. 1 (June 28, 2022): 35–54. http://dx.doi.org/10.32350/cto.21.03.
Full textAbstract:
Single Cell Omics (SCO) is an evolving field in biomedical research which offers prime application in neurosciences. The human nervous system is complex and shows variability in cell types. It includes neurons (functional components), glial cells (supporting cells), astrocytes (provide nourishment), oligodendrocytes (synthesize myelin sheath), and microglia (defense mechanism). To understand the functional and disease states of the nervous system, it is essential to investigate them at the single-cell level. It has been estimated that every 1 in 9 people is affected by mental or neurological disorders, including psychological disorders (generally referred to as mental disorders), psychotic disorders (involving psychosis), and neurological disorders (involving neurological factors), globally. These disorders have multifactorial etiology and are caused by genetic and environmental factors. Every disorder has distinct pathophysiology affecting multiple brain regions. SCO has excellent potential to provide insight regarding the diagnosis, pathophysiology, and treatment of neurological disorders. The stringent well directed SCO methods enhance the understanding of complex nervous system disorders, such as meningitis, stroke, schizophrenia, Parkinson’s disease, and Alzheimer’s disease, which paves the way for future research.
18
Todeva-Radneva, Anna, Katrin Aryutova, Sevdalina Kandilarova, Rositsa Paunova, and Drozdstoy Stoyanov. "The Translational Potential of Non-coding RNAs and Multimodal MRI Data Sets as Diagnostic and Differential Diagnostic Biomarkers for Mood Disorders." Current Topics in Medicinal Chemistry 21, no. 11 (August 4, 2021): 949–63. http://dx.doi.org/10.2174/1568026621666210521144534.
Full textAbstract:
Major Depressive Disorder (MDD) and Bipolar Disorder (BD) have a high prevalence and detrimental socio-economic consequences for the patients and the community. Furthermore, the depressive symptomatology of both disorders is essentially identical, thus rendering the clinical differential diagnosis between the two significantly more difficult considering the concomitant lack of objective biomarkers. Mood disorders are multifactorial disorders the pathophysiology of which includes genetic, epigenetic, neurobiological, neuroimmunological, structural and functional brain alterations, etc. Aberrant genetic variants as well as changed differential expression of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have been implicated in the pathophysiology of MDD and BD. MiRNAs as well as lncRNAs have regulatory and modulating functions on protein-- coding gene expression thus influencing the remodeling of the architecture, neurotransmission, immunomodulation, etc. in the Central Nervous System (CNS) which are essential in the development of psychiatric disorders including MDD and BD. Moreover, both shared and distinct structural, connectivity, task-related and metabolic features have been observed via functional magnetic resonance imaging and magnetic resonance spectroscopy, suggesting the possibility of a dimensional continuum between the two disorders instead of a categorical differentiation. Aberrant connectivity within and between the Default Mode Network, the Salience Network, Executive Network, etc. as well as dysfunctional emotion, cognitive and executive processing have been associated with mood disorders. Therefore, the aim of this review is to explore a more multidimensional framework in the scientific research of mood disorders, including epigenetic and neuroimaging data in order to shape an outline for their translational capacity in clinical practice.
19
de Jong, Simone, Stephen J. Newhouse, Hamel Patel, Sanghyuck Lee, David Dempster, Charles Curtis, Jose Paya-Cano, et al. "Immune signatures and disorder-specific patterns in a cross-disorder gene expression analysis." British Journal of Psychiatry 209, no. 3 (September 2016): 202–8. http://dx.doi.org/10.1192/bjp.bp.115.175471.
Full textAbstract:
BackgroundRecent studies point to overlap between neuropsychiatric disorders in symptomatology and genetic aetiology.AimsTo systematically investigate genomics overlap between childhood and adult attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and major depressive disorder (MDD).MethodAnalysis of whole-genome blood gene expression and genetic risk scores of 318 individuals. Participants included individuals affected with adult ADHD (n = 93), childhood ADHD (n = 17), MDD (n = 63), ASD (n = 51), childhood dual diagnosis of ADHD–ASD (n = 16) and healthy controls (n = 78).ResultsWeighted gene co-expression analysis results reveal disorder-specific signatures for childhood ADHD and MDD, and also highlight two immune-related gene co-expression modules correlating inversely with MDD and adult ADHD disease status. We find no significant relationship between polygenic risk scores and gene expression signatures.ConclusionsOur results reveal disorder overlap and specificity at the genetic and gene expression level. They suggest new pathways contributing to distinct pathophysiology in psychiatric disorders and shed light on potential shared genomic risk factors.
20
Bonilla, Francisco A. "Personalized therapy for common variable immunodeficiency." Allergy and Asthma Proceedings 41, no. 1 (January 1, 2020): 19–25. http://dx.doi.org/10.2500/aap.2020.41.190012.
Full textAbstract:
Background: Common variable immunodeficiency (CVID) represents a clinical descriptive diagnosis that was defined in the 1970s. Despite the vast increase in knowledge with regard to immune function and genetics, the pathophysiology of this disorder remains poorly understood in the majority of patients (75%); however, recent advances have led to a much clearer understanding of this heterogeneous group of disorders in the remaining 25%. These advances, along with developments in immune modulatory and reconstitution therapies, now permit sophisticated and specific targeting of therapies for individual patients. Methods: A literature review and author experience. Results: For > 50 years, immune globulin therapy has been applied to patients with CVID. There are several options open to patients, including a diversity of products and modes of administration. Stem cell therapy is increasingly applicable in patients with severe immune dysregulation. In some disorders (e.g., lipopolysaccharide-responsive and beige-like anchor protein, and cytotoxic T lymphocyte antigen 4 deficiencies), knowledge of the genetic basis and molecular pathophysiology permit targeted therapy by using small-molecule immune modulators and biologics. Conclusion: In the near future, it is likely that further advances in understanding the pathophysiology of CVID, together with ongoing development of biologics and small-molecule immune modulators will lead to additional targeted therapies for these patients.
21
Alciati, Alessandra, Angelo Reggiani, Daniela Caldirola, and Giampaolo Perna. "Human-Induced Pluripotent Stem Cell Technology: Toward the Future of Personalized Psychiatry." Journal of Personalized Medicine 12, no. 8 (August 20, 2022): 1340. http://dx.doi.org/10.3390/jpm12081340.
Full textAbstract:
The polygenic and multifactorial nature of many psychiatric disorders has hampered implementation of the personalized medicine approach in clinical practice. However, induced pluripotent stem cell (iPSC) technology has emerged as an innovative tool for patient-specific disease modeling to expand the pathophysiology knowledge and treatment perspectives in the last decade. Current technologies enable adult human somatic cell reprogramming into iPSCs to generate neural cells and direct neural cell conversion to model organisms that exhibit phenotypes close to human diseases, thereby effectively representing relevant aspects of neuropsychiatric disorders. In this regard, iPSCs reflect patient pathophysiology and pharmacological responsiveness, particularly when cultured under conditions that emulate spatial tissue organization in brain organoids. Recently, the application of iPSCs has been frequently associated with gene editing that targets the disease-causing gene to deepen the illness pathophysiology and to conduct drug screening. Moreover, gene editing has provided a unique opportunity to repair the putative causative genetic lesions in patient-derived cells. Here, we review the use of iPSC technology to model and potentially treat neuropsychiatric disorders by illustrating the key studies on a series of mental disorders, including schizophrenia, major depressive disorder, bipolar disorder, and autism spectrum disorder. Future perspectives will involve the development of organ-on-a-chip platforms that control the microenvironmental conditions so as to reflect individual pathophysiological by adjusting physiochemical parameters according to personal health data. This strategy could open new ways by which to build a disease model that considers individual variability and tailors personalized treatments.
22
Leckman, James F., Myrna M. Weissman, David L. Pauls, and Kenneth K. Kidd. "Family-Genetic Studies and Identification of Valid Diagnostic Categories in Adult and Child Psychiatry." British Journal of Psychiatry 151, no. 1 (July 1987): 39–44. http://dx.doi.org/10.1192/bjp.151.1.39.
Full textAbstract:
Family-genetic studies of child and adult psychiatric disorders have become increasingly fashionable over the past decade. The development of structured diagnostic interview schedules, the emergence of uniform diagnostic criteria such as DSM-III, and the use of refined design and analytic techniques from the field of chronic disease epidemiology have made substantial contributions to the methodology of such studies. Advances in molecular genetics, particularly our emerging capacity to perform chromosomal linkage studies throughout the human genome, have renewed hope that the constitutional underpinnings of some psychiatric disorders can be identified and that the pathophysiology of these disorders can be elucidated. Family-genetic techniques in child and adult psychiatry are discussed with a particular focus on their potential value in validating diagnostic categories spanning developmental epochs.
23
Inusa, Baba, Lewis Hsu, Neeraj Kohli, Anissa Patel, Kilali Ominu-Evbota, Kofi Anie, and Wale Atoyebi. "Sickle Cell Disease—Genetics, Pathophysiology, Clinical Presentation and Treatment." International Journal of Neonatal Screening 5, no. 2 (May 7, 2019): 20. http://dx.doi.org/10.3390/ijns5020020.
Full textAbstract:
Sickle cell disease (SCD) is a monogenetic disorder due to a single base-pair point mutation in the β-globin gene resulting in the substitution of the amino acid valine for glutamic acid in the β-globin chain. Phenotypic variation in the clinical presentation and disease outcome is a characteristic feature of the disorder. Understanding the pathogenesis and pathophysiology of the disorder is central to the choice of therapeutic development and intervention. In this special edition for newborn screening for haemoglobin disorders, it is pertinent to describe the genetic, pathologic and clinical presentation of sickle cell disease as a prelude to the justification for screening. Through a systematic review of the literature using search terms relating to SCD up till 2019, we identified relevant descriptive publications for inclusion. The scope of this review is mainly an overview of the clinical features of pain, the cardinal symptom in SCD, which present following the drop in foetal haemoglobin as young as five to six months after birth. The relative impact of haemolysis and small-vessel occlusive pathology remains controversial, a combination of features probably contribute to the different pathologies. We also provide an overview of emerging therapies in SCD.
24
Haijes, Hanneke A., Jaak Jaeken, and Peter M. Hasselt. "Hypothesis: determining phenotypic specificity facilitates understanding of pathophysiology in rare genetic disorders." Journal of Inherited Metabolic Disease 43, no. 4 (January 17, 2020): 701–11. http://dx.doi.org/10.1002/jimd.12201.
Full text
25
Li, Anna S., Jack F. Ingham, and Rachel Lennon. "Genetic Disorders of the Glomerular Filtration Barrier." Clinical Journal of the American Society of Nephrology 15, no. 12 (March 23, 2020): 1818–28. http://dx.doi.org/10.2215/cjn.11440919.
Full textAbstract:
The glomerular filtration barrier is a highly specialized capillary wall comprising fenestrated endothelial cells, podocytes, and an intervening basement membrane. In glomerular disease, this barrier loses functional integrity, allowing the passage of macromolecules and cells, and there are associated changes in both cell morphology and the extracellular matrix. Over the past 3 decades, there has been a transformation in our understanding about glomerular disease, fueled by genetic discovery, and this is leading to exciting advances in our knowledge about glomerular biology and pathophysiology. In current clinical practice, a genetic diagnosis already has important implications for management, ranging from estimating the risk of disease recurrence post-transplant to the life-changing advances in the treatment of atypical hemolytic uremic syndrome. Improving our understanding about the mechanistic basis of glomerular disease is required for more effective and personalized therapy options. In this review, we describe genotype and phenotype correlations for genetic disorders of the glomerular filtration barrier, with a particular emphasis on how these gene defects cluster by both their ontology and patterns of glomerular pathology.
26
Rodriguez-Sevilla, Juan Jose, Xavier Calvo, and Leonor Arenillas. "Causes and Pathophysiology of Acquired Sideroblastic Anemia." Genes 13, no. 9 (August 30, 2022): 1562. http://dx.doi.org/10.3390/genes13091562.
Full textAbstract:
The sideroblastic anemias are a heterogeneous group of inherited and acquired disorders characterized by anemia and the presence of ring sideroblasts in the bone marrow. Ring sideroblasts are abnormal erythroblasts with iron-loaded mitochondria that are visualized by Prussian blue staining as a perinuclear ring of green-blue granules. The mechanisms that lead to the ring sideroblast formation are heterogeneous, but in all of them, there is an abnormal deposition of iron in the mitochondria of erythroblasts. Congenital sideroblastic anemias include nonsyndromic and syndromic disorders. Acquired sideroblastic anemias include conditions that range from clonal disorders (myeloid neoplasms as myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms with ring sideroblasts) to toxic or metabolic reversible sideroblastic anemia. In the last 30 years, due to the advances in genomic techniques, a deep knowledge of the pathophysiological mechanisms has been accomplished and the bases for possible targeted treatments have been established. The distinction between the different forms of sideroblastic anemia is based on the study of the characteristics of the anemia, age of diagnosis, clinical manifestations, and the performance of laboratory analysis involving genetic testing in many cases. This review focuses on the differential diagnosis of acquired disorders associated with ring sideroblasts.
27
Fargeot, Guillaume, and Andoni Echaniz-Laguna. "Sensory neuronopathies: new genes, new antibodies and new concepts." Journal of Neurology, Neurosurgery & Psychiatry 92, no. 4 (February 9, 2021): 398–406. http://dx.doi.org/10.1136/jnnp-2020-325536.
Full textAbstract:
Degeneration of dorsal root ganglia (DRG) and its central and peripheral projections provokes sensory neuronopathy (SN), a rare disorder with multiple genetic and acquired causes. Clinically, patients with SN usually present with proprioceptive ataxia, patchy and asymmetric sensory abnormalities, widespread areflexia and no weakness. Classic causes of SN include cancer, Sjögren’s syndrome, vitamin deficiency, chemotherapy, mitochondrial disorders and Friedreich ataxia. More recently, new genetic and dysimmune disorders associated with SN have been described, including RFC1 gene-linked cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) and anti-FGFR3 antibodies. In this review, we detail the pathophysiology of DRG degeneration, and the genetic and acquired causes of SN, with a special focus on the recently described CANVAS and anti-FGFR3 antibodies. We also propose a user-friendly and easily implemented SN diagnostic strategy.
28
Gallagher, Patrick G. "Diagnosis and management of rare congenital nonimmune hemolytic disease." Hematology 2015, no. 1 (December 5, 2015): 392–99. http://dx.doi.org/10.1182/asheducation-2015.1.392.
Full textAbstract:
AbstractRare, congenital nonimmune hemolytic disorders of the erythrocyte, although uncommon, are important causes of anemia in the child and adult. These are a heterogeneous group of diseases that disrupt normal erythrocyte structure and function in varying ways. Predominant are abnormalities of hemoglobin stability, defects of erythrocyte metabolism, and disorders of erythrocyte hydration. Unstable hemoglobinopathies may lead to chronic or episodic hemolysis. Perturbation of critical enzymes of the Embden–Meyerhof pathway lead to altered erythrocyte metabolism and chronic hemolysis. Disorders of erythrocyte hydration are an under-recognized cause of hemolytic anemia. Beyond pathophysiologic mechanisms of disease, clinical, laboratory, and genetic heterogeneity characterize this group of disorders. Often, they are underdiagnosed or misdiagnosed. This review discusses pathophysiology, inheritance, clinical findings, laboratory manifestations, and management considerations in several rare nonimmune hemolytic diseases including the unstable hemoglobins, disorders of erythrocyte metabolism, and abnormalities of erythrocyte hydration.
29
Holtmann, Gerald, Ayesha Shah, and Mark Morrison. "Pathophysiology of Functional Gastrointestinal Disorders: A Holistic Overview." Digestive Diseases 35, Suppl. 1 (2017): 5–13. http://dx.doi.org/10.1159/000485409.
Full textAbstract:
Background and Summary: Traditionally, functional gastrointestinal disorders (FGID), including functional dyspepsia or irritable bowel syndrome (IBS), are defined by more or less specific symptoms and the absence of structural or biochemical abnormalities that cause these symptoms. This concept is now considered to be outdated; if appropriate tests are applied, structural or biochemical abnormalities that explain or cause the symptoms may be found in many patients. Another feature of FGID are the highly prevalent psychiatric comorbidities, such as depression and anxiety. It is implied that mood disorders “cause” gastrointestinal symptoms. In fact, epidemiological data now provide strong evidence that in subsets of cases, gastrointestinal (GI) symptoms arise first and mood disorders occur later, while in other patients the reverse appears to happen. Possible mechanisms for gut-brain dysfunction have been identified, with systemic minimal inflammation as a causal factor in at least some subjects. Other mechanisms that play a role in FGID include chronic infections, intestinal microbiota, low-grade mucosal inflammation including the increase of eosinophils, systemic immune activation, altered intestinal permeability, in diarrhea predominant IBS altered bile salt metabolism, abnormalities in the serotonin metabolism and genetic factors. All these factors might be modulated by environmental factors such as diet. Key Messages: While a number of factors can be linked to specific symptoms (e.g., pain or diarrhea), it is evident that the symptom-based categorization of patients will not allow targeted treatments that specifically address the underlying pathophysiology.
30
Famitafreshi, Hamidreza, and Morteza Karimian. "Overview of the Recent Advances in Pathophysiology and Treatment for Autism." CNS & Neurological Disorders - Drug Targets 17, no. 8 (October 2, 2018): 590–94. http://dx.doi.org/10.2174/1871527317666180706141654.
Full textAbstract:
Background & Objective: Autism is a developmental disorder that manifests itself in early childhood. Autism is characterized by inability to acquire social skills, repetitive behaviors and failure of speech and nonverbal communication development. Recent studies have shown that genetic mutations occur in majority of individuals with autism. These mutations cause a variety of disorders that ultimately lead to brain disorders. It is noteworthy that all mutations do not follow the same pattern. They encompass various kinds of mutations. Autism needs to be treated during childhood as untreated patients usually do not progress to the later stages of development. In this regard, many studies have been performed and numerous treatments have been proposed to improve the outcome of this disease. Conclusion: In this review, we have discussed new advancements made in understanding the pathophysiology of autism. Furthermore, we have also discussed new treatments which have been proposed and have successfully translated affected children. Overall, it is concluded that new advances have largely helped these patients.
31
Scorza, Manuela, Ausilia Elce, Federica Zarrilli, Renato Liguori, Felice Amato, and Giuseppe Castaldo. "Genetic Diseases That Predispose to Early Liver Cirrhosis." International Journal of Hepatology 2014 (2014): 1–11. http://dx.doi.org/10.1155/2014/713754.
Full textAbstract:
Inherited liver diseases are a group of metabolic and genetic defects that typically cause early chronic liver involvement. Most are due to a defect of an enzyme/transport protein that alters a metabolic pathway and exerts a pathogenic role mainly in the liver. The prevalence is variable, but most are rare pathologies. We review the pathophysiology of such diseases and the diagnostic contribution of laboratory tests, focusing on the role of molecular genetics. In fact, thanks to recent advances in genetics, molecular analysis permits early and specific diagnosis for most disorders and helps to reduce the invasive approach of liver biopsy.
32
Vogel, Timothy W., Calvin S. Carter, Kingsley Abode-Iyamah, Qihong Zhang, and Shenandoah Robinson. "The role of primary cilia in the pathophysiology of neural tube defects." Neurosurgical Focus 33, no. 4 (October 2012): E2. http://dx.doi.org/10.3171/2012.6.focus12222.
Full textAbstract:
Neural tube defects (NTDs) are a set of disorders that occur from perturbation of normal neural development. They occur in open or closed forms anywhere along the craniospinal axis and often result from a complex interaction between environmental and genetic factors. One burgeoning area of genetics research is the effect of cilia signaling on the developing neural tube and how the disruption of primary cilia leads to the development of NTDs. Recent progress has implicated the hedgehog (Hh), wingless-type integration site family (Wnt), and planar cell polarity (PCP) pathways in primary cilia as involved in normal neural tube patterning. A set of disorders involving cilia function, known as ciliopathies, offers insight into abnormal neural development. In this article, the authors discuss the common ciliopathies, such as Meckel-Gruber and Joubert syndromes, that are associated with NTDs, and review cilia-related signaling cascades responsible for mammalian neural tube development. Understanding the contribution of cilia in the formation of NTDs may provide greater insight into this common set of pediatric neurological disorders.
33
Skakkebaek, Niels E., Ewa Rajpert-De Meyts, Germaine M. Buck Louis, Jorma Toppari, Anna-Maria Andersson, Michael L. Eisenberg, Tina Kold Jensen, et al. "Male Reproductive Disorders and Fertility Trends: Influences of Environment and Genetic Susceptibility." Physiological Reviews 96, no. 1 (January 2016): 55–97. http://dx.doi.org/10.1152/physrev.00017.2015.
Full textAbstract:
It is predicted that Japan and European Union will soon experience appreciable decreases in their populations due to persistently low total fertility rates (TFR) below replacement level (2.1 child per woman). In the United States, where TFR has also declined, there are ethnic differences. Caucasians have rates below replacement, while TFRs among African-Americans and Hispanics are higher. We review possible links between TFR and trends in a range of male reproductive problems, including testicular cancer, disorders of sex development, cryptorchidism, hypospadias, low testosterone levels, poor semen quality, childlessness, changed sex ratio, and increasing demand for assisted reproductive techniques. We present evidence that several adult male reproductive problems arise in utero and are signs of testicular dysgenesis syndrome (TDS). Although TDS might result from genetic mutations, recent evidence suggests that it most often is related to environmental exposures of the fetal testis. However, environmental factors can also affect the adult endocrine system. Based on our review of genetic and environmental factors, we conclude that environmental exposures arising from modern lifestyle, rather than genetics, are the most important factors in the observed trends. These environmental factors might act either directly or via epigenetic mechanisms. In the latter case, the effects of exposures might have an impact for several generations post-exposure. In conclusion, there is an urgent need to prioritize research in reproductive physiology and pathophysiology, particularly in highly industrialized countries facing decreasing populations. We highlight a number of topics that need attention by researchers in human physiology, pathophysiology, environmental health sciences, and demography.
34
Bejar, Rafael, Ross Levine, and Benjamin L. Ebert. "Unraveling the Molecular Pathophysiology of Myelodysplastic Syndromes." Journal of Clinical Oncology 29, no. 5 (February 10, 2011): 504–15. http://dx.doi.org/10.1200/jco.2010.31.1175.
Full textAbstract:
Somatically acquired genetic abnormalities lead to the salient features that define myelodysplastic syndromes (MDS): clonal hematopoiesis, aberrant differentiation, peripheral cytopenias, and risk of progression to acute myeloid leukemia. Although specific karyotypic abnormalities have been linked to MDS for decades, more recent findings have demonstrated the importance of mutations within individual genes, focal alterations that are not apparent by standard cytogenetics, and aberrant epigenetic regulation of gene expression. The spectrum of genetic abnormalities in MDS implicates a wide range of molecular mechanisms in the pathogenesis of these disorders, including activation of tyrosine kinase signaling, genomic instability, impaired differentiation, altered ribosome function, and changes in the bone marrow microenvironment. Specific alterations present in individual patients with MDS may explain much of the heterogeneity in clinical phenotype associated with this disease and can predict prognosis and response to therapy. Elucidation of the full complement of genetic causes of MDS promises profound insight into the biology of the disease, improved classification and prognostic scoring schemes, and the potential for novel targeted therapies with molecular predictors of response.
35
Baldwin, Kelly J., and Cynthia M. Correll. "Prion Disease." Seminars in Neurology 39, no. 04 (August 2019): 428–39. http://dx.doi.org/10.1055/s-0039-1687841.
Full textAbstract:
AbstractPrion diseases are a phenotypically diverse set of disorders characterized by protease-resistant abnormally shaped proteins known as prions. There are three main groups of prion diseases, termed sporadic (Creutzfeldt–Jakob disease [CJD], sporadic fatal insomnia, and variably protease-sensitive prionopathy), genetic (genetic CJD, fatal familial insomnia, and Gerstmann–Straussler–Scheinker syndrome), and acquired (kuru, variant CJD, and iatrogenic CJD). This article will review the pathophysiology, genetics, clinical presentations, and diagnostic challenges in patients with prion disease. Case discussions, images, and tables will be used to highlight important characteristics of prion disease and prion mimics.
36
Zuo, Yanning, Don Wei, Carissa Zhu, Ormina Naveed, Weizhe Hong, and Xia Yang. "Unveiling the Pathogenesis of Psychiatric Disorders Using Network Models." Genes 12, no. 7 (July 20, 2021): 1101. http://dx.doi.org/10.3390/genes12071101.
Full textAbstract:
Psychiatric disorders are complex brain disorders with a high degree of genetic heterogeneity, affecting millions of people worldwide. Despite advances in psychiatric genetics, the underlying pathogenic mechanisms of psychiatric disorders are still largely elusive, which impedes the development of novel rational therapies. There has been accumulating evidence suggesting that the genetics of complex disorders can be viewed through an omnigenic lens, which involves contextualizing genes in highly interconnected networks. Thus, applying network-based multi-omics integration methods could cast new light on the pathophysiology of psychiatric disorders. In this review, we first provide an overview of the recent advances in psychiatric genetics and highlight gaps in translating molecular associations into mechanistic insights. We then present an overview of network methodologies and review previous applications of network methods in the study of psychiatric disorders. Lastly, we describe the potential of such methodologies within a multi-tissue, multi-omics approach, and summarize the future directions in adopting diverse network approaches.
37
Xiol, Clara, Maria Heredia, Ainhoa Pascual-Alonso, Alfonso Oyarzabal, and Judith Armstrong. "Technological Improvements in the Genetic Diagnosis of Rett Syndrome Spectrum Disorders." International Journal of Molecular Sciences 22, no. 19 (September 26, 2021): 10375. http://dx.doi.org/10.3390/ijms221910375.
Full textAbstract:
Rett syndrome (RTT) is a severe neurodevelopmental disorder that constitutes the second most common cause of intellectual disability in females worldwide. In the past few years, the advancements in genetic diagnosis brought by next generation sequencing (NGS), have made it possible to identify more than 90 causative genes for RTT and significantly overlapping phenotypes (RTT spectrum disorders). Therefore, the clinical entity known as RTT is evolving towards a spectrum of overlapping phenotypes with great genetic heterogeneity. Hence, simultaneous multiple gene testing and thorough phenotypic characterization are mandatory to achieve a fast and accurate genetic diagnosis. In this review, we revise the evolution of the diagnostic process of RTT spectrum disorders in the past decades, and we discuss the effectiveness of state-of-the-art genetic testing options, such as clinical exome sequencing and whole exome sequencing. Moreover, we introduce recent technological advancements that will very soon contribute to the increase in diagnostic yield in patients with RTT spectrum disorders. Techniques such as whole genome sequencing, integration of data from several “omics”, and mosaicism assessment will provide the tools for the detection and interpretation of genomic variants that will not only increase the diagnostic yield but also widen knowledge about the pathophysiology of these disorders.
38
Eloranta, Jyrki J., and Gerd A. Kullak-Ublick. "The Role of FXR in Disorders of Bile Acid Homeostasis." Physiology 23, no. 5 (October 2008): 286–95. http://dx.doi.org/10.1152/physiol.00020.2008.
Full textAbstract:
As ligands for the nuclear receptor FXR, bile acids regulate their own synthesis, transport, and conjugation, thus protecting against bile acid toxicity. Recently, the role of genetic variants in FXR itself, FXR target genes, and regulators of FXR in the pathophysiology of the liver and intestine has become increasingly evident.
39
Foreman, John. "Genetic Diseases of the Kidney." Open Urology & Nephrology Journal 8, no. 1 (November 26, 2015): 136–47. http://dx.doi.org/10.2174/1874303x015080100136.
Full textAbstract:
The number of genes associated with renal disease is increasing every day and this has led to a clearer understanding of the pathophysiology of renal disease in many disorders. It is also appreciated now that a genetic mutation(s) underlie many renal syndromes. Genetic testing may also offer the possibility to diagnose some renal diseases without the need for a renal biopsy. It also allows the prenatal diagnosis of certain renal diseases in at risk fetuses or identification of potential renal disease before it has become manifest. Finally, identification of a specific gene mutation holds the possibility of correction though gene therapy in the future. It is increasingly clear that many renal disorders in pediatrics are a consequence of genetic mutations. In the future, genetic testing will become as easy and as common as ordering a serum creatinine today.
40
Tebbi, Cameron K. "Sickle Cell Disease, a Review." Hemato 3, no. 2 (May 30, 2022): 341–66. http://dx.doi.org/10.3390/hemato3020024.
Full textAbstract:
Sickle cell disease and its variants constitute the most common inherited blood disorders affecting millions of individuals worldwide. Significant information regarding the nature of the genetic mutations and modifier genes that result in increased or decreased severity of the disease are available. In recent years, detailed data regarding molecular genetics, pathophysiology, mechanisms for the development of symptoms and side effects of sickle cell disease have been published. The relationship of physiological changes, cellular interactions, coexisting coagulation disorders, effects of association with other genetic disorders and a number of intervening factors have been explored. New techniques for pre-conception, prenatal, in utero, and neonatal screening are available. Means for prediction of the severity of the disease, clinical course of the disorder, and prevention of some of its major complications have been developed. The effects of psychosocial and environmental factors have been explored. Various therapeutic strategies including bone marrow and stem cell transplantation are currently employed in the treatment of patients with sickle cell disease. Recent progress in understanding the molecular pathways controlling mammalian erythropoiesis and globin switching, as well as advances in genome engineering, particularly the gene-editing techniques, have opened a venue for genetic-based treatment of the disease. Currently, sickle cell disease is often associated with a high rate of complications and mortality. The development of new pharmacological agents, methods for gene therapy, and alterations and modification of the coexisting genetic factors and modifiers for treatment of the disease are encouraging.
41
Jia, Fangzhi, Avi Fellner, and Kishore Raj Kumar. "Monogenic Parkinson’s Disease: Genotype, Phenotype, Pathophysiology, and Genetic Testing." Genes 13, no. 3 (March 7, 2022): 471. http://dx.doi.org/10.3390/genes13030471.
Full textAbstract:
Parkinson’s disease may be caused by a single pathogenic variant (monogenic) in 5–10% of cases, but investigation of these disorders provides valuable pathophysiological insights. In this review, we discuss each genetic form with a focus on genotype, phenotype, pathophysiology, and the geographic and ethnic distribution. Well-established Parkinson’s disease genes include autosomal dominant forms (SNCA, LRRK2, and VPS35) and autosomal recessive forms (PRKN, PINK1 and DJ1). Furthermore, mutations in the GBA gene are a key risk factor for Parkinson’s disease, and there have been major developments for X-linked dystonia parkinsonism. Moreover, atypical or complex parkinsonism may be due to mutations in genes such as ATP13A2, DCTN1, DNAJC6, FBXO7, PLA2G6, and SYNJ1. Furthermore, numerous genes have recently been implicated in Parkinson’s disease, such as CHCHD2, LRP10, TMEM230, UQCRC1, and VPS13C. Additionally, we discuss the role of heterozygous mutations in autosomal recessive genes, the effect of having mutations in two Parkinson’s disease genes, the outcome of deep brain stimulation, and the role of genetic testing. We highlight that monogenic Parkinson’s disease is influenced by ethnicity and geographical differences, reinforcing the need for global efforts to pool large numbers of patients and identify novel candidate genes.
42
Dudley, C. R., L. A. Giuffra, and S. T. Reeders. "Identifying genetic determinants in human essential hypertension." Journal of the American Society of Nephrology 3, no. 4 (October 1992): S2. http://dx.doi.org/10.1681/asn.v34s2.
Full textAbstract:
Genetic factors play an important role in the pathophysiology of human essential hypertension. The remarkable success of molecular genetic techniques in identifying the basis for single gene disorders at the DNA level has encouraged investigators to apply similar techniques in an attempt to identify blood pressure genes. In contrast to single gene disorders, however, the study of blood pressure is complicated by its quantitative, complex, heterogeneous, and polygenic nature. This article examines current methods and strategies for identifying genetic determinants in human hypertension. The availability of highly polymorphic markers, the advances in quantitative trait analysis, and the mapping of blood pressure-determining genes in a polygenic rat model of hypertension suggest that molecular genetic research in human hypertension has come of age.
43
Weener, M. E., N. A. Bakunina, J. M. Salmasi, G. V. Poryadin, D. Barh, Yu D. Kuznetsova, and L. M. Balashova. "Genetic testing of ocular manifestations of proliferative syndrome to provide pathophysiology-oriented treatment." Russian Journal of Clinical Ophthalmology 22, no. 1 (2022): 16–22. http://dx.doi.org/10.32364/2311-7729-2022-22-1-16-22.
Full textAbstract:
Background: uncontrolled cell proliferation of the ocular blood network is one of the leading causes of blindness and low vision worldwide. We summarize relevant published data and our 5-year experience in searching treatment tools for excessive non-productive proliferation. Aim: to describe genetic patterns in patients with ocular blood network proliferation for predicting disease course and selecting adequate treatment. Patients and Methods: 1210 patients with proliferative ocular disorders, retinopathy of prematurity, and diabetes were enrolled. Patients were divided into three groups: (1) monogenic disorders, (2) proliferative vitreoretinopathy and diabetes mellitus, (3) retinopathy of prematurity. Follow-up was 6 to 36 months. Laboratory, genetic, and relevant clinical tests were pursued in all patients. Results: proprietary approach of bioinformatic analysis of whole exome/whole genome sequencing data allows for specifying the proliferative process’s prognosis and severity given clinical and genetic findings. This approach includes the analysis of gene mutations directly or indirectly involved in angiogenesis and key signaling pathways. The analysis of mutation identified in group 2 revealed 509C>T TGFB1 gene polymorphism in two patients and c.3174G>A IGF1R gene polymorphism in three patients. In group 3, the most common VEGFA gene polymorphisms were +13553C>T, -634G>C, +405G>C (rs2010963), and -460C>T (rs833061). Conclusion: specifying the prognosis of the course and severity of proliferative ocular disorders pathogenically-oriented targeted treatment requires specialized genetic testing using an improved data analysis approach. Keywords: proliferative syndrome, diabetes, retinopathy of prematurity, VEGFA, TGFB1, IGF1R, Stickler syndrome, Wagner syndrome, Wolframe syndrome, Marshall syndrome, Norrie disease, Coats disease, retinoschisis. For citation: Weener M.E., Bakunina N.A., Salmasi J.M. et al. Genetic testing of ocular manifestations of proliferative syndrome to provide pathophysiology-oriented treatment. Russian Journal of Clinical Ophthalmology. 2022;22(1):16–22 (in Russ.). DOI: 10.32364/2311-7729- 2022-22-1-16-22.
44
Kobayashi, Tetsuro, and Keisuke Nagao. "Host–microbial dialogues in atopic dermatitis." International Immunology 31, no. 7 (March 16, 2019): 449–56. http://dx.doi.org/10.1093/intimm/dxz026.
Full textAbstract:
AbstractRecent advances in sequencing technologies have revealed the diversity of microbes that reside on the skin surface which has enhanced our understanding on skin as an ecosystem, wherein the epidermis, immune cells and the microbiota engage in active dialogues that maintain barrier integrity and functional immunity. This mutual dialogue is altered in atopic dermatitis (AD), in which an impaired epidermal barrier, the skin microbial flora and aberrant immunity can form a vicious cycle that leads to clinical manifestations as eczematous dermatitis. Microbiome studies have revealed an altered microbial landscape in AD and genetic studies have identified genes that underlie barrier impairment and immune dysregulation. Shifting from the long-standing notion that AD was mediated by conventional allergic responses, emerging data suggest that it is a disorder of an altered host–microbial relationship with sophisticated pathophysiology. In this review, we will discuss recent advancements that suggest the roles of the skin microbiota in AD pathophysiology, genetic factors that mediate barrier impairment, dysbiosis and inflammation. Studies in mice, classic AD and monogenic disorders that manifest as AD collectively facilitate our understanding of AD pathophysiology and provide a foundation for novel therapeutic strategies.
45
Brüggemann, Norbert. "Contemporary functional neuroanatomy and pathophysiology of dystonia." Journal of Neural Transmission 128, no. 4 (January 24, 2021): 499–508. http://dx.doi.org/10.1007/s00702-021-02299-y.
Full textAbstract:
AbstractDystonia is a disabling movement disorder characterized by abnormal postures or patterned and repetitive movements due to co-contraction of muscles in proximity to muscles desired for a certain movement. Important and well-established pathophysiological concepts are the impairment of sensorimotor integration, a loss of inhibitory control on several levels of the central nervous system and changes in synaptic plasticity. These mechanisms collectively contribute to an impairment of the gating function of the basal ganglia which results in an insufficient suppression of noisy activity and an excessive activation of cortical areas. In addition to this traditional view, a plethora of animal, genetic, imaging and electrophysiological studies highlight the role of the (1) cerebellum, (2) the cerebello-thalamic connection and (3) the functional interplay between basal ganglia and the cerebellum in the pathophysiology of dystonia. Another emerging topic is the better understanding of the microarchitecture of the striatum and its implications for dystonia. The striosomes are of particular interest as they likely control the dopamine release via inhibitory striato-nigral projections. Striosomal dysfunction has been implicated in hyperkinetic movement disorders including dystonia. This review will provide a comprehensive overview about the current understanding of the functional neuroanatomy and pathophysiology of dystonia and aims to move the traditional view of a ‘basal ganglia disorder’ to a network perspective with a dynamic interplay between cortex, basal ganglia, thalamus, brainstem and cerebellum.
46
Teggi, Roberto, Bruno Colombo, Laura Zagato, and Massimo Filippi. "Could ionic regulation disorders explain the overlap between meniere’s disease and migraine?" Journal of Vestibular Research 31, no. 4 (July 28, 2021): 297–301. http://dx.doi.org/10.3233/ves-200788.
Full textAbstract:
Ménière’s disease (MD) is an inner ear disorder characterized by a burden of symptoms and comorbidities, including migraine. In both disorders, ionic dysregulation may play a role as a predisposing factor. In recent years. aquaporins have been widely investigated, but the results are far from conclusive. We recently studied the genetics of ionic transporters and the hormone endogenous ouabain as predisposing factors for development of MD. In particular, we found two genetic polymorphisms associated with MD: 1) rs3746951, a missense variant (Gly180Ser) in the salt-inducible kinase-1 (SIK1) gene encoding a Na+, K+ ATPase; 2) rs487119, an intronic variant of gene SLC8A1 coding for a Na+, Ca++ exchanger (NCX-1). Ionic concentration in the brain also plays a role in the pathophysiology of migraine. In this brief review we summarize what has been published on MD and migraine.
47
di Biase, Lazzaro, Alessandro Di Santo, Maria Letizia Caminiti, Pasquale Maria Pecoraro, Simona Paola Carbone, and Vincenzo Di Lazzaro. "Dystonia Diagnosis: Clinical Neurophysiology and Genetics." Journal of Clinical Medicine 11, no. 14 (July 19, 2022): 4184. http://dx.doi.org/10.3390/jcm11144184.
Full textAbstract:
Dystonia diagnosis is based on clinical examination performed by a neurologist with expertise in movement disorders. Clues that indicate the diagnosis of a movement disorder such as dystonia are dystonic movements, dystonic postures, and three additional physical signs (mirror dystonia, overflow dystonia, and geste antagonists/sensory tricks). Despite advances in research, there is no diagnostic test with a high level of accuracy for the dystonia diagnosis. Clinical neurophysiology and genetics might support the clinician in the diagnostic process. Neurophysiology played a role in untangling dystonia pathophysiology, demonstrating characteristic reduction in inhibition of central motor circuits and alterations in the somatosensory system. The neurophysiologic measure with the greatest evidence in identifying patients affected by dystonia is the somatosensory temporal discrimination threshold (STDT). Other parameters need further confirmations and more solid evidence to be considered as support for the dystonia diagnosis. Genetic testing should be guided by characteristics such as age at onset, body distribution, associated features, and coexistence of other movement disorders (parkinsonism, myoclonus, and other hyperkinesia). The aim of the present review is to summarize the state of the art regarding dystonia diagnosis focusing on the role of neurophysiology and genetic testing.
48
Thein, Swee Lay. "Genetic association studies in β-hemoglobinopathies." Hematology 2013, no. 1 (December 6, 2013): 354–61. http://dx.doi.org/10.1182/asheducation-2013.1.354.
Full textAbstract:
Abstract Characterization of the molecular basis of the β-thalassemias and sickle cell disease (SCD) clearly showed that individuals with the same β-globin genotypes can have extremely diverse clinical severity. Two key modifiers, an innate ability to produce fetal hemoglobin and coinheritance of α-thalassemia, both derived from family and population studies, affect the pathophysiology of both disorders at the primary level. In the past 2 decades, scientific research had applied genetic approaches to identify additional genetic modifiers. The review summarizes recent genetic studies and key genetic modifiers identified and traces the story of fetal hemoglobin genetics, which has led to an emerging network of globin gene regulation. The discoveries have provided insights on new targets for therapeutic intervention and raise possibilities of developing fetal hemoglobin predictive diagnostics for predicting disease severity in the newborn and for integration into prenatal diagnosis to better inform genetic counseling.
49
Jain, Rakesh, Sloan Manning, and Andrew J. Cutler. "Good, better, best: clinical scenarios for the use of L-methylfolate in patients with MDD." CNS Spectrums 25, no. 6 (December 13, 2019): 750–64. http://dx.doi.org/10.1017/s1092852919001469.
Full textAbstract:
AbstractDepression is among the most prevalent mental disorders worldwide, and a substantial proportion of patients do not respond adequately to standard antidepressants. Our understanding of the pathophysiology of depression is no longer limited to the chemical imbalance of neurotransmitters, but also involves the interplay of proinflammatory modulators in the central nervous system, as well as folate metabolism. Additional factors such as stress and metabolic disorders also may contribute. Multiple inflammatory, metabolic, and genetic markers have been identified and may provide critical information to help clinicians individualize treatments for patients to achieve optimal outcomes. Recent advancements in research have clarified underlying causes of depression and have led to possible new avenues for adjunctive treatment. Among these is L-methylfolate, a medical food that is thought to enhance synthesis of monoamines (serotonin, norepinephrine, and dopamine), suppress inflammation, and promote neural health. Clinical studies that assessed supplemental use of L-methylfolate in patients with usual care-resistant depression found that it resulted in improved outcomes. Patients with selective serotonin reuptake inhibitor-resistant depression, and particularly subgroups with biomarkers of inflammation or metabolic disorders or folate metabolism-related genetic polymorphisms (or ≥2 of these factors), had the best responses. Considering this, the goals of this review are to 1) highlight recent advances in the pathophysiology of major depressive disorder as it pertains to folate and associated biomarkers and 2) establish the profiles of patients with depression who could benefit most from supplemental use of L-methylfolate.
50
Gerges, Perla, Tania Bitar, Frederic Laumonnier, Sylviane Marouillat, Georges Nemer, Christian R. Andres, and Walid Hleihel. "Identification of Novel Gene Variants for Autism Spectrum Disorders in the Lebanese Population Using Whole-Exome Sequencing." Genes 13, no. 2 (January 21, 2022): 186. http://dx.doi.org/10.3390/genes13020186.
Full textAbstract:
In our previous study, in which array CGH was used on 19 Lebanese ASD subjects and their parents, we identified rare copy number variants (CNVs) in 14 subjects. The five remaining subjects did not show any CNVs related to autism spectrum disorders (ASD). In the present complementary study, we applied whole-exome sequencing (WES), which allows the identification of rare genetic variations such as single nucleotide variations and small insertions/deletions, to the five negative CNV subjects. After stringent filtering of initial data on the five families, three novel genes potentially related to neurodevelopment were identified, including a de novo mutation in the MIS18BP1 gene. In addition, genes already known to be related to ASD contained sequence variations. Our findings outline the potential involvement of the novel de novo mutation in the MIS18BP1 gene in the genetic etiology and pathophysiology of ASD and highlights the genetic complexity of these disorders. Further studies with larger cohorts of subjects are needed to confirm these observations, and functional analyses need to be performed to understand the precise pathophysiology in these cases.