The history of medical genetics is briefly reviewed. It is evident that medical genetics with its inseparable part, clinical genetics, started out as a cfinical science from the very beginning. Its robust development ...The history of medical genetics is briefly reviewed. It is evident that medical genetics with its inseparable part, clinical genetics, started out as a cfinical science from the very beginning. Its robust development in the developed countries is the result of a close interaction between the basic sciences and clinical genetics. In China, however, clinical genetics has not received due emphasis and medical genetics is still not recognized as one of the medical specialties. This is in marked contrast to the situation in the West. It is high time to acknowledge that medical genetics is a medical specialty and to promote clinical genetics service in qualified hospitals in our country.展开更多
Objective To draw a conclusion from the experience on the integrated curriculum of medical genetics and embryonic development set up for the eight-year clinical medicine,and to lay the foundation for its application t...Objective To draw a conclusion from the experience on the integrated curriculum of medical genetics and embryonic development set up for the eight-year clinical medicine,and to lay the foundation for its application to the five-year clinical medicine. Methods The advantages and disadvantages of the integrated curriculumof medical genetics and embryonic development were analyzed with the comparative analysis method. And opinions of students of the eight-year clinical medicine on the teaching of the current integrated curriculum were learnt about with questionnaires. Results The current integrated curriculum of medical genetics and embryonic development has basically achieved the goal of simplifying the original teaching contents and the crossing and integration of the related discipline contents,the overall student satisfaction is high. Conclusion The integrated curriculum of medical genetics and embryonic development is helpful for the integral optimization of the medical curriculum framework,which can be expanded to the five-year clinical medicine in the future.展开更多
Background: According to the World Health Organization, the worldwide prevalence of infertility is 17.5%. The male share of responsibility is undeniable. Several factors, such as smoking, alcoholism, obesity and envir...Background: According to the World Health Organization, the worldwide prevalence of infertility is 17.5%. The male share of responsibility is undeniable. Several factors, such as smoking, alcoholism, obesity and environmental pollution are sources of infertility in men. The aim of this study was to determine the spermological profile of infertile men and the factors associated with sperm parameter abnormalities. Methods: This retrospective study analysed 1000 sperm samples over an 11-year period, from January 2010 to December 2021. Results: The average age was 37.52 ± 8.66 years. Surgical history of varicocele and teratozoospermia were associated (p-value = 0.0001). Candida albicans was associated with a 2.27-fold risk of necrozoospermia and a 3.14-fold risk of oligozoospermia. The link between the reason for requesting a spermogram and the age range between 38 and 47 was significant (p-value Conclusion: Today, lifestyle and environmental pollution play a major role in sperm parameter abnormalities.展开更多
BACKGROUND Familial adenomatous polyposis(FAP)is a disorder of autosomal dominant inheritance that is responsible for around 1%of colorectal cancer(CRC)cases.AIM To determine the mutation profile of FAP-specific to th...BACKGROUND Familial adenomatous polyposis(FAP)is a disorder of autosomal dominant inheritance that is responsible for around 1%of colorectal cancer(CRC)cases.AIM To determine the mutation profile of FAP-specific to the Hungarian population.METHODS This prospective single-center study enrolled patients with clinically suspected FAP or attenuated FAP(aFAP).Whole-exome next-generation sequencing was performed to detect variants of 50 FAP priority genes and 173 CRC predisposing genes or other CRC disease-associated genes.To identify larger deletions and insertions,a multiplex amplifiable probe hybridization technique was used.The identified genes were then classified according to the American College of Medical Genetics and Genomics guidelines.RESULTS A total of 26 index patients with clinically suspected FAP(n=21)and aFAP(n=5)were enrolled.APC gene alterations were confirmed in 92.31%of the cases(region 1B deletion,n=2;whole-gene deletion,n=4;frameshift mutation,n=2;nonsense mutation,n=5,and splice mutation,n=1),with the remaining two cases having CHEK2 and MSH3 gene alterations.According to pathogenicity,21 cases had pathogenic mutations,6 cases had likely pathogenic mutations,and 16 cases had variants of unknown significance(VUS).The most frequent of the latter were the POLE(n=5)and PIEZO1(n=4)gene variants.CONCLUSION Germline mutations in the APC gene were confirmed in more than 90%of Hungarian patients with clinically suspected FAP.Although the role of VUS genes is unclear,they are highly likely to play a role in the development of CRC.展开更多
Gallbladder cancer is a malignancy of biliary tract which is infrequent in developed countries but common in some specific geographical regions of developing countries. Late diagnosis and deprived prognosis are major ...Gallbladder cancer is a malignancy of biliary tract which is infrequent in developed countries but common in some specific geographical regions of developing countries. Late diagnosis and deprived prognosis are major problems for treatment of gallbladder carcinoma. The dramatic associations of this orphan cancer with various genetic and environmental factors are responsible for its poorly defined pathogenesis. An understanding to the relationship between epidemiology, molecular genetics and pathogenesis of gallbladder cancer can add new insights to its undetermined pathophysiology. Present review article provides a recent update regarding epidemiology, pathogenesis, and molecular genetics of gallbladder cancer. We systematically reviewed published literature on gallbladder cancer from online search engine Pub Med(http://www.ncbi.nlm.nih.gov/pubmed). Various keywords used for retrieval of articles were Gallbladder, cancer Epidemiology, molecular genetics and bullion operators like AND, OR, NOT. Cross references were manually searched from various online search engines(http://www.ncbi.nlm.nih.gov/pubmed,https://scholar.google.co.in/, http://www.medline.com/home.jsp). Most of the articles published from 1982 to 2015 in peer reviewed journals have been included in this review.展开更多
Vitiligo is an acquired disease characterized principally by patchy depigmentation of skin and overlying hair. Generalized vitiligo （GV）, the predominant form of the disorder, results from autoimmune loss of melanoc...Vitiligo is an acquired disease characterized principally by patchy depigmentation of skin and overlying hair. Generalized vitiligo （GV）, the predominant form of the disorder, results from autoimmune loss of melanocytes from affected regions. GV is a ＂complex trait＂, inherited in a non-Mendelian polygenic, multifactorial manner. GV is epidemiologically associated with other autoimmune diseases, both in GV patients and in their close relatives, suggesting that shared genes underlie susceptibility to this group of diseases. Early candidate gene association studies yielded a few successes, such as PTPN22, but most such reports now appear to be false-positives. Subsequent genomewide linkage studies identified NLRP1 and XBP1, apparent true GV susceptibility genes involved in immune regulation, and recent genome-wide association studies （GWAS） of GV in Caucasian and Chinese populations have yielded a large number of additional validated GV susceptibility genes. Together, these genes highlight biological systems and pathways that reach from the immune cells to the melanocyte, and provide insights into both disease pathogenesis and potential new targets for both treatment and even prevention of GV and other autoimmune diseases in genetically susceptible individuals.展开更多
Epigenetic mechanisms, including DNA methylation, are responsible for determining and maintaining cell fate, stably differentiating the various tissues in our bodies. Increasing evidence shows that DNA methylation pla...Epigenetic mechanisms, including DNA methylation, are responsible for determining and maintaining cell fate, stably differentiating the various tissues in our bodies. Increasing evidence shows that DNA methylation plays a significant role in cancer, from the silencing of tumor suppressors to the activation of oncogenes and the promotion of metastasis. Recent studies also suggest a role for DNA methylation in drug resistance. This perspective article discusses how DNA methylation may contribute to the development of acquired endocrine resistance, with a focus on breast cancer. In addition, we discuss DNA methylome profiling and how recent developments in this field are shedding new light on the role of epigenetics in endocrine resistance. Hormone ablation is the therapy of choice for hormone-sensitive breast tumors, yet as many as 40% of patients inevitably relapse, and these hormone refractory tumors often have a poor prognosis. Epigenetic studies could provide DNA methylation biomarkers to predict and diagnose acquired resistance in response to treatment. Elucidation of epigenetic mechanisms may also lead to the development of new treatments that specifically target epigenetic abnormalities or vulnerabilities in cancer cells. Expectations must be tempered by the fact that epigenetic mechanisms of endocrine resistance remain poorly understood, and further study is required to better understand how altering epigenetic pathways with therapeutics can promote or inhibit endocrine resistance in different contexts. Going forward, DNA methylome profiling will become increasingly central to epigenetic research, heralding a network-based approach to epigenetics that promises to advance our understanding of the etiology of cancer in ways not previously possible.展开更多
Arrhythmogenic right ventricular cardiomyopathy(ARVC) is a genetic disease characterized by myocyte loss and fibro-fatty tissue replacement. Diagnosis of ARVC remains a clinical challenge mainly at its early stages an...Arrhythmogenic right ventricular cardiomyopathy(ARVC) is a genetic disease characterized by myocyte loss and fibro-fatty tissue replacement. Diagnosis of ARVC remains a clinical challenge mainly at its early stages and in patients with minimal echocardiographic right ventricular(RV) abnormalities. ARVC shares some common features with other cardiac diseases, such as RV outflow ventricular tachycardia, Brugada syndrome, and myocarditis, due to arrhythmic expressivity and biventricular involvement. The identification of ARVC can be often challenging, because of the heterogeneous clinical presentation, highly variable intra- and inter-family expressivity and incomplete penetrance. This genotypephenotype "plasticity" is largely unexplained. A familial history of ARVC is present in 30% to 50% of cases, and the disease is considered a genetic cardiomyopathy, usually inherited in an autosomal dominant pattern with variable penetrance and expressivity; in addition, autosomal recessive forms have been reported(Naxos disease and Carvajal syndrome). Diagnosis of ARVC relays on a scoring system, with major or minorcriteria on the Revised Task Force Criteria. Implantable cardioverter defibrillators(ICDs) are increasingly utilized in patients with ARVC who have survived sudden death(SD)(secondary prevention). However, there are few data available to help identifying ARVC patients in whom the prophylactic implantation of an ICD is truly warranted. Prevention of SD is the primary goal of management. Pharmacologic treatment of arrhythmias, catheter ablation of ventricular tachycardia, and ICD are the mainstay of treatment of ARVC.展开更多
Cardiovascular diseases are affected by multiple factors like genetic as well as environmental hence they reveal factorial nature. The evidences that genetic factors are susceptible for developing cardiovascular disea...Cardiovascular diseases are affected by multiple factors like genetic as well as environmental hence they reveal factorial nature. The evidences that genetic factors are susceptible for developing cardiovascular diseases come from twin studies and familial aggregation. Different ethnic populations reveal differences in the prevalence coronary artery disease(CAD) pointing towards the genetic susceptibility. With progression in molecular techniques different developments have been made to comprehend the disease physiology. Molecular markers have also assisted to recognize genes that may provide evidences to evaluate the role of genetic factors in causation of susceptibility towards CAD. Numerous studies suggest the contribution of specific "candidate genes", which correlate with various roles/pathways that are involved in the coronary heart disease. Different studies have revealed that there are large numbers of genes which are involved towards the predisposition of CAD. However, these reports are not consistent. One of the reasons could be weak contribution of genetic susceptibility of these genes. Genome wide associations show different chromosomal locations which dock, earlier unknown, genes which may attribute to CAD. In the present review different ApoAI-CⅡI-AIV gene clusters have been discussed.展开更多
Mitochondria are cytoplasmic organelles referred to as the powerhouse of the cell because they are primarily involved in oxidative phosphorylation and energy production.They are particularly abundant in tissues with h...Mitochondria are cytoplasmic organelles referred to as the powerhouse of the cell because they are primarily involved in oxidative phosphorylation and energy production.They are particularly abundant in tissues with high energy demands,including muscle,liver,and brain,and mitochondrial dysfunction,oxidative mitochondrial DNA(mtDNA)damage,and impaired mitochondrial dynamics have often been associated with neurodegeneration.展开更多
Paroxysmal kinesigenic dyskinesia(PKD),the most common type of paroxysmal movement disorder,is characterized by sudden and brief attacks of choreoathetosis or dystonia triggered by sudden voluntary movements.PKD is ma...Paroxysmal kinesigenic dyskinesia(PKD),the most common type of paroxysmal movement disorder,is characterized by sudden and brief attacks of choreoathetosis or dystonia triggered by sudden voluntary movements.PKD is mainly caused by mutations in the PRRT2 or TMEM151A gene.The exact pathophysiological mechanisms of PKD remain unclear,although the function of PRRT2 protein has been well characterized in the last decade.Based on abnormal ion channels and disturbed synaptic transmission in the absence of PRRT2,PKD may be channelopathy or synaptopathy,or both.In addition,the cerebellum is regarded as the key pathogenic area.Spreading depolarization in the cerebellum is tightly associated with dyskinetic episodes.Whereas,in PKD,other than the cerebellum,the role of the cerebrum including the cortex and thalamus needs to be further investigated.展开更多
Background Type 2 diabetes(T2D)is a chronic metabolic disorder with high comorbidity with mental disorders.The genetic links between attention-deficit/hyperactivity disorder(ADHD)and T2D have yet to be elucidated.Aims...Background Type 2 diabetes(T2D)is a chronic metabolic disorder with high comorbidity with mental disorders.The genetic links between attention-deficit/hyperactivity disorder(ADHD)and T2D have yet to be elucidated.Aims We aim to assess shared genetics and potential associations between ADHD and T2D.Methods We performed genetic correlation,two-sample Mendelian randomisation and polygenic overlap analyses between ADHD and T2D.The genome-wide association study(GWAS)summary results of T2D(80154 cases and 853816 controls),ADHD2019(20183 cases and 35191 controls from the 2019 GWAS ADHD dataset)and ADHD2022(38691 cases and 275986 controls from the 2022 GWAS ADHD dataset)were used for the analyses.The T2D dataset was obtained from the DIAGRAM Consortium.The ADHD datasets were obtained from the Psychiatric Genomics Consortium.We compared genome-wide association signals to reveal shared genetic variation between T2D and ADHD using the larger ADHD2022 dataset.Moreover,molecular pathways were constructed based on large-scale literature data to understand the connection between ADHD and T2D.Results T2D has positive genetic correlations with ADHD2019(rg=0.33)and ADHD2022(rg=0.31).Genetic liability to ADHD2019 was associated with an increased risk for T2D(odds ratio(OR):1.30,p<0.001),while genetic liability to ADHD2022 had a suggestive causal effect on T2D(OR:1.30,p=0.086).Genetic liability to T2D was associated with a higher risk for ADHD2019(OR:1.05,p=0.001)and ADHD2022(OR:1.03,p<0.001).The polygenic overlap analysis showed that most causal variants of T2D are shared with ADHD2022.T2D and ADHD2022 have three overlapping loci.Molecular pathway analysis suggests that ADHD and T2D could promote the risk of each other through inflammatory pathways.Conclusions Our study demonstrates substantial shared genetics and bidirectional causal associations between ADHD and T2D.展开更多
Pharmacogenetics and pharmacogenomics deal with the role of genetic factors in drug effectiveness and adverse drug reactions. The promise of a personalized medicine is beginning to be explored but requires much more c...Pharmacogenetics and pharmacogenomics deal with the role of genetic factors in drug effectiveness and adverse drug reactions. The promise of a personalized medicine is beginning to be explored but requires much more clinical and translational research. Specific DNA abnormalities in some cancers already have led to effective targeted treatments. Racially determined frequency differences in pharmacogenetic traits may affect choice of treatment requiring specific testing rather than basing treatments according to racial designation. The role of genes in variable responses to foreign chemicals (xenobiotics) has been termed ecogenetics or toxicogenetics raising problems in public health and occupational medicine. Nutrigenetics refers to genetic variation in response to nutrients and may affect nutritional requirements and predisposition to chronic disease.展开更多
Circadian rhythm alterations have been implicated in multiple neuropsychiatric disorders,particularly those of sleep,addiction,anxiety,and mood. Circadian rhythms are known to be maintained by a set of classic clock g...Circadian rhythm alterations have been implicated in multiple neuropsychiatric disorders,particularly those of sleep,addiction,anxiety,and mood. Circadian rhythms are known to be maintained by a set of classic clock genes that form complex mutual and self-regulatory loops. While many other genes showing rhythmic expression have been identified by genome-wide studies,their roles in circadian regulation remain largely unknown. In attempts to directly connect circadian rhythms with neuropsychiatric disorders,genetic studies have identifi ed gene mutations associated with several rare sleep disorders or sleep-related traits. Other than that,genetic studies of circadian genes in psychiatric disorders have had limited success. As an important mediator of environmental factors and regulators of circadian rhythms,the epigenetic system may hold the key to the etiology or pathology of psychiatric disorders,their subtypes or endophenotypes. Epigenomic regulation of the circadian system and the related changes have not been thoroughly explored in the context of neuropsychiatric disorders. We argue for systematic investigation of the circadian system,particularly epigenetic regulation,and its involvement in neuropsychiatric disorders to improve our understanding of human behavior and disease etiology.展开更多
Oral cancer(OC)is one of the most recurrent cancers in the head and neck squamous cancer(SCCHN)category.Recently,the genome-wide association studies(GWAS)have gained growing interest in the scientific community.GWAS h...Oral cancer(OC)is one of the most recurrent cancers in the head and neck squamous cancer(SCCHN)category.Recently,the genome-wide association studies(GWAS)have gained growing interest in the scientific community.GWAS have identified several pathways involved in the interactions among general risk factors and genomic variants affecting SCCHN.This systematic overview aims to critically evaluate the latest data reported within the scientific literature.The aim was to investigate the impact of genetic aspects on SCCHN onset and prognosis,involving other clinical and systemic co-factors.PubMed,Google Scholar,and Cancer Genetics Web databases have been systematically investigated for original articles published in the last two years,reporting studies on the main queries addressed in this work.This review also comparatively describes the impact of environmental and pathological co-factors in different types of cancers,clarifying and updating the role of genetic factors in SCCHN onset and development.The main outcomes reported may be helpful to drive clinicians towards their clinical evaluations for the most appropriate therapeutic approach in SCCHN.展开更多
The identification of genes increasing one’s risk of developing common,complex disorders like Parkinson’s disease(PD)can provide novel therapeutic opportunities.A prime example of this are the consequences of mutati...The identification of genes increasing one’s risk of developing common,complex disorders like Parkinson’s disease(PD)can provide novel therapeutic opportunities.A prime example of this are the consequences of mutations in GBA1,the gene responsible for the lysosomal storage disorder Gaucher disease(GD).GD is a multi-system disorder,primarily affecting tissues of the reticuloendothelial system.A subset of patients with GD also have neuronopathic manifestations(types 2 and 3 GD).展开更多
Purpose: To alert the medical community that whole exome sequencing can find accessory gene changes in well-known syndromes that alter preventive health care and management. Meaning: A collagen type VI gene change add...Purpose: To alert the medical community that whole exome sequencing can find accessory gene changes in well-known syndromes that alter preventive health care and management. Meaning: A collagen type VI gene change adds muscle weakness, hypermobility, and dysautonomia concerns to usual management considerations for Down syndrome. Methods: Commercial whole exome sequencing combined with clinical interpretation of DNA sequence change added new considerations to patient management and parental counsel. Results: An 11-year-old child with the trisomy 21 form of Down syndrome who was evaluated for extraordinary joint laxity had a heterozygous collagen type VI aspartic to glutamic acid (COL6A3 c.6360 C>G p.Asp2120Glu) gene change found by whole exome sequencing. The DNA variant was qualified as having strong relevance to the enhanced hypermobility due to prior association of collagen 6 gene changes with myopathy. Conclusions: Dual diagnosis of Ehlers-Danlos syndrome was not assigned because the patient lacked criteria like bruising, unusual scars, or selected dysautonomia symptoms. The concept of a hypermobility spectrum offers advantages for management of its constituent conditions if clinically guided ascertainment and DNA diagnostics are employed.展开更多
The goal of this review is to explain the requirement for understanding the genetic structure of infertility arising from male factor and to discuss the essentials of these genetic elements(2). The majority of the pop...The goal of this review is to explain the requirement for understanding the genetic structure of infertility arising from male factor and to discuss the essentials of these genetic elements(2). The majority of the population is affected by this disorder caused by male factor infertility(1); but the etiologies are still unknown. After the primary genetic structure in infertile phenotypes is searched, an evaluation can be made. Thus the reasons causing infertility can be discovered and patients can benefit from effective therapies(1). Publications about male infertility within the recent 10 years in the Pubmed database were discussed(1). There are some approachments for describing the function of specificgenes, but no adequate study is present to be useful for diagnosing and treating male infertility(1). Male fertility and fertility in offspring of males are considerably affected by the exact transition of epigenetic information(1). When the genetic factors playing a role in male infertility were analysed, significant steps will be taken for treating patients and determining the reasons of idiopathic infertility(1). Developments in technology associated with the impact of genetics may enable to specify the etiology of male infertility by determining specific infertile phenotype marks(1).展开更多
Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective d...Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial cells.The biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even urine.Among these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and muscles.Neurofilament light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and sensitivity.However,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal injury.Glial fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration rate.TAR DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related research.Evidence is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease prognosis.Despite the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable challenge.This review summarizes the latest research achievements concerning blood biomarkers in amyotrophic lateral sclerosis that can provide a more direct basis for the differential diagnosis and prognostic assessment of the disease beyond a reliance on clinical manifestations and electromyography findings.展开更多
Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism....Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.展开更多
文摘The history of medical genetics is briefly reviewed. It is evident that medical genetics with its inseparable part, clinical genetics, started out as a cfinical science from the very beginning. Its robust development in the developed countries is the result of a close interaction between the basic sciences and clinical genetics. In China, however, clinical genetics has not received due emphasis and medical genetics is still not recognized as one of the medical specialties. This is in marked contrast to the situation in the West. It is high time to acknowledge that medical genetics is a medical specialty and to promote clinical genetics service in qualified hospitals in our country.
基金financially supported by Medical Education Research at Shanghai Jiao Tong University School of Medicine(YB150632)Projects for Course and Textbook Construction in 2015 and Shanghai Key Course Construction Project(2015-37-59)
文摘Objective To draw a conclusion from the experience on the integrated curriculum of medical genetics and embryonic development set up for the eight-year clinical medicine,and to lay the foundation for its application to the five-year clinical medicine. Methods The advantages and disadvantages of the integrated curriculumof medical genetics and embryonic development were analyzed with the comparative analysis method. And opinions of students of the eight-year clinical medicine on the teaching of the current integrated curriculum were learnt about with questionnaires. Results The current integrated curriculum of medical genetics and embryonic development has basically achieved the goal of simplifying the original teaching contents and the crossing and integration of the related discipline contents,the overall student satisfaction is high. Conclusion The integrated curriculum of medical genetics and embryonic development is helpful for the integral optimization of the medical curriculum framework,which can be expanded to the five-year clinical medicine in the future.
文摘Background: According to the World Health Organization, the worldwide prevalence of infertility is 17.5%. The male share of responsibility is undeniable. Several factors, such as smoking, alcoholism, obesity and environmental pollution are sources of infertility in men. The aim of this study was to determine the spermological profile of infertile men and the factors associated with sperm parameter abnormalities. Methods: This retrospective study analysed 1000 sperm samples over an 11-year period, from January 2010 to December 2021. Results: The average age was 37.52 ± 8.66 years. Surgical history of varicocele and teratozoospermia were associated (p-value = 0.0001). Candida albicans was associated with a 2.27-fold risk of necrozoospermia and a 3.14-fold risk of oligozoospermia. The link between the reason for requesting a spermogram and the age range between 38 and 47 was significant (p-value Conclusion: Today, lifestyle and environmental pollution play a major role in sperm parameter abnormalities.
基金Supported by the Research Grants of the National Research,Development and Innovation Office,No.K125377,No.K134863 and No.K143549New National Excellence Program of the Ministry of Human Capacities,No.UNKP-20-5-SZTE-161,No.UNKP-22-3-SZTE-233,No.UNKP-23-5-SZTE-719,No.UNKP-22-4-SZTE-296 and No.UNKP-22-3-SZTE-278+1 种基金Janos Bolyai Research Grant,No.BO/00723/22the Géza Hetényi Research Grant by Albert Szent-Györgyi Medical School,University of Szeged.
文摘BACKGROUND Familial adenomatous polyposis(FAP)is a disorder of autosomal dominant inheritance that is responsible for around 1%of colorectal cancer(CRC)cases.AIM To determine the mutation profile of FAP-specific to the Hungarian population.METHODS This prospective single-center study enrolled patients with clinically suspected FAP or attenuated FAP(aFAP).Whole-exome next-generation sequencing was performed to detect variants of 50 FAP priority genes and 173 CRC predisposing genes or other CRC disease-associated genes.To identify larger deletions and insertions,a multiplex amplifiable probe hybridization technique was used.The identified genes were then classified according to the American College of Medical Genetics and Genomics guidelines.RESULTS A total of 26 index patients with clinically suspected FAP(n=21)and aFAP(n=5)were enrolled.APC gene alterations were confirmed in 92.31%of the cases(region 1B deletion,n=2;whole-gene deletion,n=4;frameshift mutation,n=2;nonsense mutation,n=5,and splice mutation,n=1),with the remaining two cases having CHEK2 and MSH3 gene alterations.According to pathogenicity,21 cases had pathogenic mutations,6 cases had likely pathogenic mutations,and 16 cases had variants of unknown significance(VUS).The most frequent of the latter were the POLE(n=5)and PIEZO1(n=4)gene variants.CONCLUSION Germline mutations in the APC gene were confirmed in more than 90%of Hungarian patients with clinically suspected FAP.Although the role of VUS genes is unclear,they are highly likely to play a role in the development of CRC.
文摘Gallbladder cancer is a malignancy of biliary tract which is infrequent in developed countries but common in some specific geographical regions of developing countries. Late diagnosis and deprived prognosis are major problems for treatment of gallbladder carcinoma. The dramatic associations of this orphan cancer with various genetic and environmental factors are responsible for its poorly defined pathogenesis. An understanding to the relationship between epidemiology, molecular genetics and pathogenesis of gallbladder cancer can add new insights to its undetermined pathophysiology. Present review article provides a recent update regarding epidemiology, pathogenesis, and molecular genetics of gallbladder cancer. We systematically reviewed published literature on gallbladder cancer from online search engine Pub Med(http://www.ncbi.nlm.nih.gov/pubmed). Various keywords used for retrieval of articles were Gallbladder, cancer Epidemiology, molecular genetics and bullion operators like AND, OR, NOT. Cross references were manually searched from various online search engines(http://www.ncbi.nlm.nih.gov/pubmed,https://scholar.google.co.in/, http://www.medline.com/home.jsp). Most of the articles published from 1982 to 2015 in peer reviewed journals have been included in this review.
基金supported in part by the grants R01 AR45585 and R01 AR056292 from the National Institutes of Health,USA
文摘Vitiligo is an acquired disease characterized principally by patchy depigmentation of skin and overlying hair. Generalized vitiligo （GV）, the predominant form of the disorder, results from autoimmune loss of melanocytes from affected regions. GV is a ＂complex trait＂, inherited in a non-Mendelian polygenic, multifactorial manner. GV is epidemiologically associated with other autoimmune diseases, both in GV patients and in their close relatives, suggesting that shared genes underlie susceptibility to this group of diseases. Early candidate gene association studies yielded a few successes, such as PTPN22, but most such reports now appear to be false-positives. Subsequent genomewide linkage studies identified NLRP1 and XBP1, apparent true GV susceptibility genes involved in immune regulation, and recent genome-wide association studies （GWAS） of GV in Caucasian and Chinese populations have yielded a large number of additional validated GV susceptibility genes. Together, these genes highlight biological systems and pathways that reach from the immune cells to the melanocyte, and provide insights into both disease pathogenesis and potential new targets for both treatment and even prevention of GV and other autoimmune diseases in genetically susceptible individuals.
基金supported in part by National Institutes of Health grants U01ES015986, U54 CA113001 and R01CA069065This TL1 award was funded by Award Number KL2 RR025754 from the National Center for Research Resources
文摘Epigenetic mechanisms, including DNA methylation, are responsible for determining and maintaining cell fate, stably differentiating the various tissues in our bodies. Increasing evidence shows that DNA methylation plays a significant role in cancer, from the silencing of tumor suppressors to the activation of oncogenes and the promotion of metastasis. Recent studies also suggest a role for DNA methylation in drug resistance. This perspective article discusses how DNA methylation may contribute to the development of acquired endocrine resistance, with a focus on breast cancer. In addition, we discuss DNA methylome profiling and how recent developments in this field are shedding new light on the role of epigenetics in endocrine resistance. Hormone ablation is the therapy of choice for hormone-sensitive breast tumors, yet as many as 40% of patients inevitably relapse, and these hormone refractory tumors often have a poor prognosis. Epigenetic studies could provide DNA methylation biomarkers to predict and diagnose acquired resistance in response to treatment. Elucidation of epigenetic mechanisms may also lead to the development of new treatments that specifically target epigenetic abnormalities or vulnerabilities in cancer cells. Expectations must be tempered by the fact that epigenetic mechanisms of endocrine resistance remain poorly understood, and further study is required to better understand how altering epigenetic pathways with therapeutics can promote or inhibit endocrine resistance in different contexts. Going forward, DNA methylome profiling will become increasingly central to epigenetic research, heralding a network-based approach to epigenetics that promises to advance our understanding of the etiology of cancer in ways not previously possible.
文摘Arrhythmogenic right ventricular cardiomyopathy(ARVC) is a genetic disease characterized by myocyte loss and fibro-fatty tissue replacement. Diagnosis of ARVC remains a clinical challenge mainly at its early stages and in patients with minimal echocardiographic right ventricular(RV) abnormalities. ARVC shares some common features with other cardiac diseases, such as RV outflow ventricular tachycardia, Brugada syndrome, and myocarditis, due to arrhythmic expressivity and biventricular involvement. The identification of ARVC can be often challenging, because of the heterogeneous clinical presentation, highly variable intra- and inter-family expressivity and incomplete penetrance. This genotypephenotype "plasticity" is largely unexplained. A familial history of ARVC is present in 30% to 50% of cases, and the disease is considered a genetic cardiomyopathy, usually inherited in an autosomal dominant pattern with variable penetrance and expressivity; in addition, autosomal recessive forms have been reported(Naxos disease and Carvajal syndrome). Diagnosis of ARVC relays on a scoring system, with major or minorcriteria on the Revised Task Force Criteria. Implantable cardioverter defibrillators(ICDs) are increasingly utilized in patients with ARVC who have survived sudden death(SD)(secondary prevention). However, there are few data available to help identifying ARVC patients in whom the prophylactic implantation of an ICD is truly warranted. Prevention of SD is the primary goal of management. Pharmacologic treatment of arrhythmias, catheter ablation of ventricular tachycardia, and ICD are the mainstay of treatment of ARVC.
文摘Cardiovascular diseases are affected by multiple factors like genetic as well as environmental hence they reveal factorial nature. The evidences that genetic factors are susceptible for developing cardiovascular diseases come from twin studies and familial aggregation. Different ethnic populations reveal differences in the prevalence coronary artery disease(CAD) pointing towards the genetic susceptibility. With progression in molecular techniques different developments have been made to comprehend the disease physiology. Molecular markers have also assisted to recognize genes that may provide evidences to evaluate the role of genetic factors in causation of susceptibility towards CAD. Numerous studies suggest the contribution of specific "candidate genes", which correlate with various roles/pathways that are involved in the coronary heart disease. Different studies have revealed that there are large numbers of genes which are involved towards the predisposition of CAD. However, these reports are not consistent. One of the reasons could be weak contribution of genetic susceptibility of these genes. Genome wide associations show different chromosomal locations which dock, earlier unknown, genes which may attribute to CAD. In the present review different ApoAI-CⅡI-AIV gene clusters have been discussed.
文摘Mitochondria are cytoplasmic organelles referred to as the powerhouse of the cell because they are primarily involved in oxidative phosphorylation and energy production.They are particularly abundant in tissues with high energy demands,including muscle,liver,and brain,and mitochondrial dysfunction,oxidative mitochondrial DNA(mtDNA)damage,and impaired mitochondrial dynamics have often been associated with neurodegeneration.
基金supported by grants from the National Natural Science Foundation(81330025).
文摘Paroxysmal kinesigenic dyskinesia(PKD),the most common type of paroxysmal movement disorder,is characterized by sudden and brief attacks of choreoathetosis or dystonia triggered by sudden voluntary movements.PKD is mainly caused by mutations in the PRRT2 or TMEM151A gene.The exact pathophysiological mechanisms of PKD remain unclear,although the function of PRRT2 protein has been well characterized in the last decade.Based on abnormal ion channels and disturbed synaptic transmission in the absence of PRRT2,PKD may be channelopathy or synaptopathy,or both.In addition,the cerebellum is regarded as the key pathogenic area.Spreading depolarization in the cerebellum is tightly associated with dyskinetic episodes.Whereas,in PKD,other than the cerebellum,the role of the cerebrum including the cortex and thalamus needs to be further investigated.
文摘Background Type 2 diabetes(T2D)is a chronic metabolic disorder with high comorbidity with mental disorders.The genetic links between attention-deficit/hyperactivity disorder(ADHD)and T2D have yet to be elucidated.Aims We aim to assess shared genetics and potential associations between ADHD and T2D.Methods We performed genetic correlation,two-sample Mendelian randomisation and polygenic overlap analyses between ADHD and T2D.The genome-wide association study(GWAS)summary results of T2D(80154 cases and 853816 controls),ADHD2019(20183 cases and 35191 controls from the 2019 GWAS ADHD dataset)and ADHD2022(38691 cases and 275986 controls from the 2022 GWAS ADHD dataset)were used for the analyses.The T2D dataset was obtained from the DIAGRAM Consortium.The ADHD datasets were obtained from the Psychiatric Genomics Consortium.We compared genome-wide association signals to reveal shared genetic variation between T2D and ADHD using the larger ADHD2022 dataset.Moreover,molecular pathways were constructed based on large-scale literature data to understand the connection between ADHD and T2D.Results T2D has positive genetic correlations with ADHD2019(rg=0.33)and ADHD2022(rg=0.31).Genetic liability to ADHD2019 was associated with an increased risk for T2D(odds ratio(OR):1.30,p<0.001),while genetic liability to ADHD2022 had a suggestive causal effect on T2D(OR:1.30,p=0.086).Genetic liability to T2D was associated with a higher risk for ADHD2019(OR:1.05,p=0.001)and ADHD2022(OR:1.03,p<0.001).The polygenic overlap analysis showed that most causal variants of T2D are shared with ADHD2022.T2D and ADHD2022 have three overlapping loci.Molecular pathway analysis suggests that ADHD and T2D could promote the risk of each other through inflammatory pathways.Conclusions Our study demonstrates substantial shared genetics and bidirectional causal associations between ADHD and T2D.
文摘Pharmacogenetics and pharmacogenomics deal with the role of genetic factors in drug effectiveness and adverse drug reactions. The promise of a personalized medicine is beginning to be explored but requires much more clinical and translational research. Specific DNA abnormalities in some cancers already have led to effective targeted treatments. Racially determined frequency differences in pharmacogenetic traits may affect choice of treatment requiring specific testing rather than basing treatments according to racial designation. The role of genes in variable responses to foreign chemicals (xenobiotics) has been termed ecogenetics or toxicogenetics raising problems in public health and occupational medicine. Nutrigenetics refers to genetic variation in response to nutrients and may affect nutritional requirements and predisposition to chronic disease.
基金supported by grants to CL from the NIH,USA (R01-ES024988 and U01-MH103340)the Central South University of China
文摘Circadian rhythm alterations have been implicated in multiple neuropsychiatric disorders,particularly those of sleep,addiction,anxiety,and mood. Circadian rhythms are known to be maintained by a set of classic clock genes that form complex mutual and self-regulatory loops. While many other genes showing rhythmic expression have been identified by genome-wide studies,their roles in circadian regulation remain largely unknown. In attempts to directly connect circadian rhythms with neuropsychiatric disorders,genetic studies have identifi ed gene mutations associated with several rare sleep disorders or sleep-related traits. Other than that,genetic studies of circadian genes in psychiatric disorders have had limited success. As an important mediator of environmental factors and regulators of circadian rhythms,the epigenetic system may hold the key to the etiology or pathology of psychiatric disorders,their subtypes or endophenotypes. Epigenomic regulation of the circadian system and the related changes have not been thoroughly explored in the context of neuropsychiatric disorders. We argue for systematic investigation of the circadian system,particularly epigenetic regulation,and its involvement in neuropsychiatric disorders to improve our understanding of human behavior and disease etiology.
文摘Oral cancer(OC)is one of the most recurrent cancers in the head and neck squamous cancer(SCCHN)category.Recently,the genome-wide association studies(GWAS)have gained growing interest in the scientific community.GWAS have identified several pathways involved in the interactions among general risk factors and genomic variants affecting SCCHN.This systematic overview aims to critically evaluate the latest data reported within the scientific literature.The aim was to investigate the impact of genetic aspects on SCCHN onset and prognosis,involving other clinical and systemic co-factors.PubMed,Google Scholar,and Cancer Genetics Web databases have been systematically investigated for original articles published in the last two years,reporting studies on the main queries addressed in this work.This review also comparatively describes the impact of environmental and pathological co-factors in different types of cancers,clarifying and updating the role of genetic factors in SCCHN onset and development.The main outcomes reported may be helpful to drive clinicians towards their clinical evaluations for the most appropriate therapeutic approach in SCCHN.
文摘The identification of genes increasing one’s risk of developing common,complex disorders like Parkinson’s disease(PD)can provide novel therapeutic opportunities.A prime example of this are the consequences of mutations in GBA1,the gene responsible for the lysosomal storage disorder Gaucher disease(GD).GD is a multi-system disorder,primarily affecting tissues of the reticuloendothelial system.A subset of patients with GD also have neuronopathic manifestations(types 2 and 3 GD).
文摘Purpose: To alert the medical community that whole exome sequencing can find accessory gene changes in well-known syndromes that alter preventive health care and management. Meaning: A collagen type VI gene change adds muscle weakness, hypermobility, and dysautonomia concerns to usual management considerations for Down syndrome. Methods: Commercial whole exome sequencing combined with clinical interpretation of DNA sequence change added new considerations to patient management and parental counsel. Results: An 11-year-old child with the trisomy 21 form of Down syndrome who was evaluated for extraordinary joint laxity had a heterozygous collagen type VI aspartic to glutamic acid (COL6A3 c.6360 C>G p.Asp2120Glu) gene change found by whole exome sequencing. The DNA variant was qualified as having strong relevance to the enhanced hypermobility due to prior association of collagen 6 gene changes with myopathy. Conclusions: Dual diagnosis of Ehlers-Danlos syndrome was not assigned because the patient lacked criteria like bruising, unusual scars, or selected dysautonomia symptoms. The concept of a hypermobility spectrum offers advantages for management of its constituent conditions if clinically guided ascertainment and DNA diagnostics are employed.
文摘The goal of this review is to explain the requirement for understanding the genetic structure of infertility arising from male factor and to discuss the essentials of these genetic elements(2). The majority of the population is affected by this disorder caused by male factor infertility(1); but the etiologies are still unknown. After the primary genetic structure in infertile phenotypes is searched, an evaluation can be made. Thus the reasons causing infertility can be discovered and patients can benefit from effective therapies(1). Publications about male infertility within the recent 10 years in the Pubmed database were discussed(1). There are some approachments for describing the function of specificgenes, but no adequate study is present to be useful for diagnosing and treating male infertility(1). Male fertility and fertility in offspring of males are considerably affected by the exact transition of epigenetic information(1). When the genetic factors playing a role in male infertility were analysed, significant steps will be taken for treating patients and determining the reasons of idiopathic infertility(1). Developments in technology associated with the impact of genetics may enable to specify the etiology of male infertility by determining specific infertile phenotype marks(1).
文摘Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial cells.The biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even urine.Among these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and muscles.Neurofilament light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and sensitivity.However,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal injury.Glial fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration rate.TAR DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related research.Evidence is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease prognosis.Despite the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable challenge.This review summarizes the latest research achievements concerning blood biomarkers in amyotrophic lateral sclerosis that can provide a more direct basis for the differential diagnosis and prognostic assessment of the disease beyond a reliance on clinical manifestations and electromyography findings.
基金supported by the Research Project of the Shanghai Health Commission,No.2020YJZX0111(to CZ)the National Natural Science Foundation of China,Nos.82021002(to CZ),82272039(to CZ),82171252(to FL)+1 种基金a grant from the National Health Commission of People’s Republic of China(PRC),No.Pro20211231084249000238(to JW)Medical Innovation Research Project of Shanghai Science and Technology Commission,No.21Y11903300(to JG).
文摘Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.
