scholarly journals Potential therapeutic targets for olfactory dysfunction in ciliopathies beyond single gene replacement

2021 ◽  
Author(s):  
Chao Xie ◽  
Jeffrey R Martens
Keyword(s):  
Wide Spectrum ◽  
Genetic Disorders ◽  
Single Gene ◽  
Therapeutic Targets ◽  
Gene Replacement ◽  
Olfactory Dysfunction ◽  
Symptomatic Therapy ◽  
Olfactory Cilia ◽  
Organ Systems ◽  
Targeted Gene Replacement

Abstract Olfactory dysfunction is a common disorder in the general population. There are multiple causes, one of which being ciliopathies, an emerging class of human hereditary genetic disorders characterized by multiple symptoms due to defects in ciliary biogenesis, maintenance, and/or function. Mutations/deletions in a wide spectrum of ciliary genes have been identified to cause ciliopathies. Currently, besides symptomatic therapy, there is no available therapeutic treatment option for olfactory dysfunction caused by ciliopathies. Multiple studies have demonstrated that targeted gene replacement can restore the morphology and function of olfactory cilia in olfactory sensory neurons and further re-establish the odor-guided behaviors in animals. Therefore, targeted gene replacement could be potentially used to treat olfactory dysfunction in ciliopathies. However, due to the potential limitations of single gene therapy for polygenic mutation-induced diseases, alternative therapeutic targets for broader curative measures need to be developed for olfactory dysfunction, and also for other symptoms in ciliopathies. Here we review the current understanding of ciliogenesis and maintenance of olfactory cilia. Furthermore, we emphasize signaling mechanisms that may be involved in the regulation of olfactory ciliary length and highlight potential alternative therapeutic targets for the treatment of ciliopathy induced dysfunction in the olfactory system and even in other ciliated organ systems.

scholarly journals Spectrum of genetic disorders and the impact on health care delivery: an introduction

1999 ◽  
Vol 5 (6) ◽  
pp. 1188-1195
Author(s):  
v El Hazmi
Keyword(s):  
Health Care ◽  
Health Care Delivery ◽  
Care Delivery ◽  
Genetic Disorders ◽  
Single Gene ◽  
Medical Attention ◽  
World Population ◽  
Symptomatic Therapy ◽  
Specialist Care ◽  
The Impact

Until recently, infectious diseases and malnutrition-related disorders constituted the major cause of ill health and mortality in the world population. However, advances in treatment of such disorders and increased understanding of the molecular basis of heredity have led to genetically transmitted conditions becoming a major cause of morbidity and mortality. Several disorders, including chromosomal [Down syndrome, Turner syndrome], single-gene [sickle-cell disease, thalassaemia, glucose-6-phosphate dehydrogenase deficiency, haemophilia, inborn errors of metabolism]and multifactorial disorders [coronary artery disease, arteriosclerosis, diabetes mellitus, hypertension, obesity]are common and becoming increasingly important. As there is no agreed-upon definitive cure with acceptable risk, these disorders are a significant burden on the health care delivery system. This is because the chronic nature of genetic diseases requires lifelong medical attention, expensive supportive and symptomatic therapy and specialist care. This review outlines the genetic disorders, their impact on health care delivery systems and the general framework required to prevent and control these disorders

Pathophysiology and therapy for haemoglobinopathies; Part II: thalassaemias

2006 ◽  
Vol 8 (10) ◽  
pp. 1-26 ◽  
Author(s):  
Fabrizia Urbinati ◽  
Catherine Madigan ◽  
Punam Malik
Keyword(s):  
Single Gene ◽  
Globin Gene ◽  
Marrow Transplant ◽  
World Population ◽  
Symptomatic Therapy ◽  
Globin Genes ◽  
Cell Disease ◽  
Critical Function ◽  
Single Gene Disorders ◽  
Clinical Syndromes

Thalassaemias result from mutations of the globin genes that cause reduced or absent haemoglobin production and thus interfere with the critical function of oxygen delivery. They represent the most common single-gene disorders, with 4.83% of the world population carrying globin gene variants. Reduced or absent α-globin (α-thalassaemia) or β-globin (β-thalassaemia) leads to anaemia and multifaceted clinical syndromes. In this second of two reviews on the pathophysiology of haemoglobinopathies, we describe the clinical features, pathophysiology and molecular basis of α- and β-thalassaemias. We then discuss current targeted therapies, including the new oral iron chelators, which, along with chronic transfusions, constitute the mainstay of symptomatic therapy for the majority of patients. Finally, we describe potentially curative therapies, such as bone marrow transplant, and discuss some of the outstanding research studies and questions, including the upcoming field of gene therapy for β-thalassaemia. An accompanying article on haemoglobinopathies (Part I) focuses on sickle cell disease.

Hyper-eosinophilic syndrome: An uncommon cause of chronic abdominal pain in an elderly male

2021 ◽  
pp. 004947552098776
Author(s):  
Dibya L Praharaj ◽  
Bipadabhanjan Mallick ◽  
Preetam Nath ◽  
Sarat C Panigrahi ◽  
Anil C Anand ◽  
...  
Keyword(s):  
Abdominal Pain ◽  
Wide Spectrum ◽  
Hypereosinophilic Syndrome ◽  
Connective Tissue Disorder ◽  
Sleep Apnoea ◽  
Chronic Abdominal Pain ◽  
Elderly Male ◽  
Essentially Normal ◽  
Organ Systems ◽  
Obstructive Sleep

Hypereosinophilia is defined as an absolute eosinophil count of ≥1.5 × 109/L, and its presence with involvement of at least one organ system defines the hypereosinophilic syndrome. It may occur with parasitic infestation, connective tissue disorder or rarely in clonal disorders such as eosinophilic leucaemia. Organ systems that may be involved include the cardiovascular, central nervous, respiratory and gastrointestinal systems. In the latter, a wide spectrum of clinical presentation may be seen from trivial, to debilitating or rarely fatal. We report an elderly male with a history of bronchial asthma, obstructive sleep apnoea and food allergy who presented with chronic abdominal pain and weight loss. Abdominal examination and routine evaluation were essentially normal other than a peripheral hyper-eosinophilia. We witnessed a brisk and lasting response to an elimination diet and corticosteroids.

Reaching Future Scientists, Consumers, & Citizens

2014 ◽  
Vol 76 (6) ◽  
pp. 379-383 ◽  
Author(s):  
Melissa A. Hicks ◽  
Rebecca J. Cline ◽  
Angela M. Trepanier
Keyword(s):  
Personalized Medicine ◽  
Genetic Basis ◽  
Genetic Disorders ◽  
Single Gene ◽  
Personal Health ◽  
Adult Onset ◽  
Biology Textbooks ◽  
Multifactorial Diseases ◽  
Single Gene Disorders

An understanding of how genomics information, including information about risk for common, multifactorial disease, can be used to promote personal health (personalized medicine) is becoming increasingly important for the American public. We undertook a quantitative content analysis of commonly used high school textbooks to assess how frequently the genetic basis of common multifactorial diseases was discussed compared with the “classic” chromosomal–single gene disorders historically used to teach the concepts of genetics and heredity. We also analyzed the types of conditions or traits that were discussed. We identified 3957 sentences across 11 textbooks that addressed multifactorial and “classic” genetic disorders. “Classic” gene disorders were discussed relatively more frequently than multifactorial diseases, as was their genetic basis, even after we enriched the sample to include five adult-onset conditions common in the general population. Discussions of the genetic or hereditary components of multifactorial diseases were limited, as were discussions of the environmental components of these conditions. Adult-onset multifactorial diseases are far more common in the population than chromosomal or single-gene disorders; many are potentially preventable or modifiable. As such, they are targets for personalized medical approaches. The limited discussion in biology textbooks of the genetic basis of multifactorial conditions and the role of environment in modifying genetic risk may limit the public’s understanding and use of personalized medicine.

scholarly journals A Homeobox Gene Is Essential for Conidiogenesis of the Rice Blast Fungus Magnaporthe oryzae

2010 ◽  
Vol 23 (4) ◽  
pp. 366-375 ◽  
Author(s):  
Wende Liu ◽  
Shiyong Xie ◽  
Xinhua Zhao ◽  
Xin Chen ◽  
Wenhui Zheng ◽  
...  
Keyword(s):  
Magnaporthe Oryzae ◽  
Rice Blast ◽  
Homeobox Gene ◽  
Gene Replacement ◽  
Fungal Genome ◽  
Protein Signaling ◽  
Homeodomain Proteins ◽  
Conidial Production ◽  
Targeted Gene Replacement ◽  
Severity Of The Disease

Magnaporthe oryzae starts its infection by the attachment of pyriform conidia on rice tissues, and severity of the disease epidemic is proportional to the quantity of conidia produced in the rice blast lesions. However, the mechanism of conidial production is not well understood. Homeodomain proteins play critical roles in regulating various growth and developmental processes in fungi and other eukaryotes. Through targeted gene replacement, we find that deletion of HTF1, one of seven homeobox genes in the fungal genome, does not affect mycelial growth but causes total defect of conidial production. Further observation revealed that the Δhtf1 mutant produces significantly more conidiophores, which curve slightly near the tip but could not develop sterigmata-like structures. Although the Δhtf1 mutant fails to form conidia, it could still develop melanized appressoria from hyphal tips and infect plants. The expression level of HTF1 is significantly reduced in the Δmgb1 G-β and ΔcpkA deletion mutant, and the ACR1 but not CON7 gene that encodes transcription factor required for normal conidiogenesis is significantly downregulated in the Δhtf1 mutant. These data suggest that the HTF1 gene is essential for conidiogenesis, and may be functionally related to the trimeric G-protein signaling and other transcriptional regulators that are known to be important for conidiation in M. oryzae.

scholarly journals The Ophthalmological Manifestations of Various Inborn Errors of Metabolism: A Narrative Review

2021 ◽  
Vol 9 (2) ◽  
pp. 137-144
Author(s):  
Abdolreza Medghalchi ◽  
◽  
Afagh Hassanzadeh Rad ◽  
Setila Dalili ◽  
◽  
...  
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Genetic Disorders ◽  
Single Gene ◽  
Scientific Information ◽  
Narrative Review ◽  
Inborn Errors ◽  
Relevant Evidence ◽  
Ocular Manifestations ◽  
Inherited Metabolic Disorders

Context: Inborn errors of metabolism or Inherited Metabolic Disorders (IMD) are a class of genetic disorders that occur because of single-gene defects. Evidence Acquisition: In this narrative review article, the authors searched Institute for Scientific Information (ISI), Web of Science, PubMed, and Google Scholar for the relevant evidence. Results: The ocular manifestations of IMDs can be distinguished in different diseases such as Albinism, Cystinosis, Homocystinuria, and Sulfite oxidize deficiency, Mannosidosis, Fucosidosis, Sialidosis, etc. Conclusions: Due to the direct toxic mechanisms of abnormal metabolites on eyes and regarding the effect of eye monitoring on the follow-up, management, and treatment, a detailed ophthalmological assessment is essential.

scholarly journals Immunogenetics of the Ocular Anterior Segment: Lessons from Inherited Disorders

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Jasmine Y. Serpen ◽  
Stephen T. Armenti ◽  
Lev Prasov
Keyword(s):  
Immune System ◽  
Lupus Erythematosus ◽  
Genetic Disorders ◽  
Anterior Segment ◽  
Adaptive Immune System ◽  
Mendelian Inheritance ◽  
Ocular Involvement ◽  
Inherited Disorders ◽  
Molecular Features ◽  
Organ Systems

Autoimmune and autoinflammatory diseases cause morbidity in multiple organ systems including the ocular anterior segment. Genetic disorders of the innate and adaptive immune system present an avenue to study more common inflammatory disorders and host-pathogen interactions. Many of these Mendelian disorders have ophthalmic manifestations. In this review, we highlight the ophthalmic and molecular features of disorders of the innate immune system. A comprehensive literature review was performed using PubMed and the Online Mendelian Inheritance in Man databases spanning 1973–2020 with a focus on three specific categories of genetic disorders: RIG-I-like receptors and downstream signaling, inflammasomes, and RNA processing disorders. Tissue expression, clinical associations, and animal and functional studies were reviewed for each of these genes. These genes have broad roles in cellular physiology and may be implicated in more common conditions with interferon upregulation including systemic lupus erythematosus and type 1 diabetes. This review contributes to our understanding of rare inherited conditions with ocular involvement and has implications for further characterizing the effect of perturbations in integral molecular pathways.

scholarly journals Varied presentations of cutaneous vasculitis: a case series

2020 ◽  
Vol 8 (8) ◽  
pp. 3066
Author(s):  
Pinky Gupta ◽  
Shweta Ganorkar ◽  
Surekha Bhalekar ◽  
Rajiv Rao
Keyword(s):  
Blood Vessels ◽  
Histopathological Examination ◽  
Wide Spectrum ◽  
Systemic Disease ◽  
Case Series ◽  
Clinical Severity ◽  
Cutaneous Vasculitis ◽  
Venous Stasis ◽  
Duration Of Symptoms ◽  
Organ Systems

Vasculitis involves a wide spectrum of clinicopathological process with reactive damage to the involved blood vessels. There is loss of vessel integrity instigating haemorrhage & luminal compromise leading to ischemia and necrosis of the tissue supplied by the involved vessels. It may affect varied size and type of blood vessels at different locations. It may be primary or secondary to systemic disease. It may involve a single organ like skin or may involve different organ systems at the same time. This case series include six cases of cutaneous vasculitis affecting different organs with varied presentations. Skin biopsies of six patients with unusual presentations were studied. Their complete history, physical examinations, laboratory investigations including serology were analysed and correlated with histopathological findings. The patients presented with different duration of symptoms varying from as short as 15 days to 1 year. Skin lesions were present in all cases while cardiac manifestation was seen in one. Serology and autoimmune disease markers were negative in all cases except one. However, histopathological features were in concordance with the clinical diagnosis of vasculitis. They were further classified as vasculitis secondary to Churg Strauss syndrome, venous stasis, Henoch Schonlein purpura or leucocytoclastic vasculitis.Vasculitis though a rare disease may manifest as an acute or chronic condition. It needs timely diagnosis by histopathological examination to aid in further management. It is important to assess the clinical severity in primary and secondary vasculitis, as it determines morbidity and mortality.

scholarly journals The spectrum and prevalence of genetic pathology among children and adolescents of the northern districts of kharkiv region

2019 ◽  
Keyword(s):  
Children And Adolescents ◽  
Human Genetics ◽  
Pediatric Population ◽  
Genetic Disorders ◽  
Single Gene ◽  
Modern Human ◽  
Chromosomal Disorders ◽  
Healthcare Facilities ◽  
Single Gene Disorders ◽  
Epidemiological Characteristics

The spectrum and prevalence of genetic pathology among the population of a certain region are determined by the founder effect and microevolution factors and, therefore, are not always comparable in different countries. The study of these indicators is an important trend of modern human genetics. The purpose of the research was to study genetic and epidemiological characteristics of the pediatric population of two northern districts of the Kharkiv region, Ukraine: Bogodukhiv and Vovchansk. Total number of children aged 0–17 was 6896 in Bogodukhiv district, and 7891 in Vovchansk district on 01/01/2016. The medical records of 307 patients were analyzed in healthcare facilities of both districts and the city of Kharkiv. The subject of the study was the cases of single-gene and chromosomal diseases. The burden of genetic disorders among children and adolescents was 0.30% in both districts. The prevalence of single-gene diseases in these districts was 0.24% in Bogodukhiv district and 0.25% in Vovchansk district. There were 9 and 12 single-gene disorders with different modes of inheritance, respectively. Only two of them were common in the districts: congenital hypothyroidism and sensorineural hearing loss. The incidence of the latter is 1:985 in Bogodukhiv district and 1:1578 in Vovchansk district. Chromosomal pathology was detected in 0.06% of the patients in Bogodukhiv district and 0.05% in Vovchansk district. Down syndrome was the only nosological form of chromosomal disorders in both districts. For other five areas of Kharkiv region, the prevalence of genetic pathology ranges from 0.36% in Izyum district to 0.47% in Balakliia and Blyzniuky as have been previously reported. The incidence of single-gene disorders is 0.27% in Izyum and 0.39% in Blyzniuky, while the incidence of chromosomal disorders varies from 0.07% in Zmiiv to 0.13% in Krasnohrad. Thus, the spectrum and prevalence of single-gene and chromosomal pathology in Bogodukhiv and Vovchansk districts correspond to those in other districts of Kharkiv region and most European countries.

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