Background:Bitter taste receptors(Tas2rs)are generally considered to sense various bitter compounds to escape the intake of toxic substances.Bitter taste receptors have been found to widely express in extraoral tissue...Background:Bitter taste receptors(Tas2rs)are generally considered to sense various bitter compounds to escape the intake of toxic substances.Bitter taste receptors have been found to widely express in extraoral tissues and have important physiological functions outside the gustatory system in vivo.Methods:To investigate the physiological functions of the bitter taste receptor cluster Tas2r106/Tas2r104/Tas2r105/Tas2r114 in lingual and extraoral tissues,multiple Tas2rs mutant mice and Gnat3 were produced using CRISPR/Cas9 gene-editing technique.A mixture containing Cas9 and sgRNA mRNAs for Tas2rs and Gnat3 gene was microinjected into the cytoplasm of the zygotes.Then,T7EN1 assays and sequencing were used to screen genetic mutation at the target sites in founder mice.Quantitative real-time polymerase chain reaction(qRT-PCR)and immunostaining were used to study the expression level of taste signaling cascade and bitter taste receptor in taste buds.Perception to taste substance was also studied using twobottle preference tests.Results:We successfully produced several Tas2rs and Gnat3 mutant mice using the CRISPR/Cas9 technique.Immunostaining results showed that the expression of GNAT3 and PLCB2 was not altered in Tas2rs mutant mice.But qRT-PCR results revealed the changed expression profile of m Tas2rs gene in taste buds of these mutant mice.With two-bottle preference tests,these mutant mice eliminate responses to cycloheximide due to genetic mutation of Tas2r105.In addition,these mutant mice showed a loss of taste perception to quinine dihydrochloride,denatonium benzoate,and cucurbitacin B(CuB).Gnat3-mediated taste receptor and its signal pathway contribute to CuB perception.Conclusions:These findings implied that these mutant mice would be a valuable means to understand the biological functions of TAS2Rs in extraoral tissues and investigate bitter compound-induced responses mediated by these TAS2Rs in many extraoral tissues.展开更多
BACKGROUND Pancreatic cancer(PC)is one of the deadliest malignancies with an alarming mortality rate.Despite significant advancement in diagnostics and therapeutics,early diagnosis remains elusive causing poor prognos...BACKGROUND Pancreatic cancer(PC)is one of the deadliest malignancies with an alarming mortality rate.Despite significant advancement in diagnostics and therapeutics,early diagnosis remains elusive causing poor prognosis,marred by mutations and epigenetic modifications in key genes which contribute to disease progression.AIM To evaluate the various biological tumor markers collectively for early diagnosis which could act as prognostic biomarkers and helps in future therapeutics of PC in Kashmir valley.METHODS A total of 50 confirmed PC cases were included in the study to evaluate the levels of carbohydrate antigen 19-9(CA 19-9),tissue polypeptide specific antigen(TPS),carcinoembryonic antigen(CEA),vascular endothelial growth factor-A(VEGF-A),and epidermal growth factor receptor(EGFR).Mutational analysis was performed to evaluate the mutations in Kirsten rat sarcoma(KRAS),Breast cancer type 2(BRCA-2),and deleted in pancreatic cancer-4(DPC-4)genes.However,epigenetic modifications(methylation of CpG islands)were performed in the promoter regions of cyclin-dependent kinase inhibitor 2A(p16;CDKN2A),MutL homolog 1(hMLH1),and Ras association domain-containing protein 1(RASSF1A)genes.RESULTS We found significantly elevated levels of biological markers CA 19-9(P≤0.05),TPS(P≤0.05),CEA(P≤0.001),and VEGF(P≤0.001).Molecular genetic analysis revealed that KRAS gene mutation is predominant in codon 12(16 subjects,P≤0.05),and 13(12 subjects,P≤0.05).However,we did not find a mutation in DPC-4(1203G>T)and BRCA-2(617delT)genes.Furthermore,epigenetic modification revealed that CpG methylation in 21(P≤0.05)and 4 subjects in the promoter regions of the p16 and hMLH1 gene,respectively.CONCLUSION In conclusion,CA 19-9,TPS,CEA,and VEGF levels were significantly elevated and collectively have potential as diagnostic and prognostic markers in PC.Global data of mutation in the KRAS gene commonly in codon 12 and rare in codon 13 could augment the predisposition towards PC.Additionally,methylation of the p16 gene could also modulate transcription of genes thereby increasing the predisposition and susceptibility towards PC.展开更多
BACKGROUND Polyostotic fibrous dysplasia(PFD)is an uncommon developmental bone disease in which normal bone and marrow are replaced by pseudotumoral tissue.The etiology of PFD is unclear,but it is generally thought to...BACKGROUND Polyostotic fibrous dysplasia(PFD)is an uncommon developmental bone disease in which normal bone and marrow are replaced by pseudotumoral tissue.The etiology of PFD is unclear,but it is generally thought to be caused by sporadic,post-zygotic mutations in the GNAS gene.Herein,we report the case of a young female with bone pain and lesions consistent with PFD,unique physical findings,and gene mutations.CASE SUMMARY A 27-year-old female presented with unbearable bone pain in her left foot for 4 years.Multiple bone lesions were detected by radiographic examinations,and a diagnosis of PFD was made after a biopsy of her left calcaneus with symptoms including pre-axial polydactyly on her left hand and severe ophthalmological problems such as high myopia,vitreous opacity,and choroidal atrophy.Her serum cortisol level was high,consistent with Cushing syndrome.Due to consanguineous marriage of her grandparents,boosted whole exome screening was performed to identify gene mutations.The results revealed mutations in HSPG2 and RIMS1,which may be contributing factors to her unique findings.CONCLUSION The unique findings in this patient with PFD may be related to mutations in the HSPG2 and RIMS1 genes.展开更多
Ce rebral palsy is a diagnostic term utilized to describe a group of permanent disorders affecting movement and posture.Patients with cerebral palsy are often only capable of limited activity,resulting from non-progre...Ce rebral palsy is a diagnostic term utilized to describe a group of permanent disorders affecting movement and posture.Patients with cerebral palsy are often only capable of limited activity,resulting from non-progressive disturbances in the fetal or neonatal brain.These disturbances severely impact the child’s daily life and impose a substantial economic burden on the family.Although cerebral palsy encompasses various brain injuries leading to similar clinical outcomes,the unde rstanding of its etiological pathways remains incomplete owing to its complexity and heterogeneity.This review aims to summarize the current knowledge on the genetic factors influencing cerebral palsy development.It is now widely acknowledged that genetic mutations and alterations play a pivotal role in cerebral palsy development,which can be further influenced by environmental fa ctors.Des pite continuous research endeavors,the underlying fa ctors contributing to cerebral palsy remain are still elusive.However,significant progress has been made in genetic research that has markedly enhanced our comprehension of the genetic factors underlying cerebral palsy development.Moreove r,these genetic factors have been categorized based on the identified gene mutations in patients through clinical genotyping,including thrombosis,angiogenesis,mitochondrial and oxidative phosphorylation function,neuronal migration,and cellular autophagy.Furthermore,exploring targeted genotypes holds potential for precision treatment.In conclusion,advancements in genetic research have substantially improved our understanding of the genetic causes underlying cerebral palsy.These breakthroughs have the potential to pave the way for new treatments and therapies,consequently shaping the future of cerebral palsy research and its clinical management.The investigation of cerebral palsy genetics holds the potential to significantly advance treatments and management strategies.By elucidating the underlying cellular mechanisms,we can develop to rgeted interventions to optimize outcomes.A continued collaboration between researchers and clinicians is imperative to comprehensively unravel the intricate genetic etiology of cerebral palsy.展开更多
Monogenic diabetes is caused by one or even more genetic variations,which may be uncommon yet have a significant influence and cause diabetes at an early age.Monogenic diabetes affects 1%to 5%of children,and early det...Monogenic diabetes is caused by one or even more genetic variations,which may be uncommon yet have a significant influence and cause diabetes at an early age.Monogenic diabetes affects 1%to 5%of children,and early detection and genetically focused treatment of neonatal diabetes and maturity-onset diabetes of the young can significantly improve long-term health and well-being.The etiology of monogenic diabetes in childhood is primarily attributed to genetic variations affecting the regulatory genes responsible for beta-cell activity.In rare instances,mutations leading to severe insulin resistance can also result in the development of diabetes.Individuals diagnosed with specific types of monogenic diabetes,which are commonly found,can transition from insulin therapy to sulfonylureas,provided they maintain consistent regulation of their blood glucose levels.Scientists have successfully devised materials and methodologies to distinguish individuals with type 1 or 2 diabetes from those more prone to monogenic diabetes.Genetic screening with appropriate findings and interpretations is essential to establish a prognosis and to guide the choice of therapies and management of these interrelated ailments.This review aims to design a comprehensive literature summarizing genetic insights into monogenetic diabetes in children and adolescents as well as summarizing their diagnosis and management.展开更多
Sotos syndrome is characterized by overgrowth features and is caused by alterations in the nuclear receptor binding SET domain protein 1 gene.Attentiondeficit/hyperactivity disorder(ADHD)is considered a neurodevelopme...Sotos syndrome is characterized by overgrowth features and is caused by alterations in the nuclear receptor binding SET domain protein 1 gene.Attentiondeficit/hyperactivity disorder(ADHD)is considered a neurodevelopment and psychiatric disorder in childhood.Genetic characteristics and clinical presentation could play an important role in the diagnosis of Sotos syndrome and ADHD.Magnetic resonance imaging(MRI)has been used to assess medical images in Sotos syndrome and ADHD.The images process is considered to display in MRI while wavelet fusion has been used to integrate distinct images for achieving more complete information in single image in this editorial.In the future,genetic mechanisms and artificial intelligence related to medical images could be used in the clinical diagnosis of Sotos syndrome and ADHD.展开更多
Bemisia tabaci （Gennadius） is a species complex, and its two most damaging biotypes B and Q are globally distributed pests. Despite increasing biological and economic impacts, little is known about the evolutionary ...Bemisia tabaci （Gennadius） is a species complex, and its two most damaging biotypes B and Q are globally distributed pests. Despite increasing biological and economic impacts, little is known about the evolutionary mechanisms that favor their competition with native populations. Here, we investigated the genetic mutations in the P450 gene of the invasive B, Q biotypes and the native Cv population. Four mutations associated with chemical resistance, Pro-Leu, Ala-Ser, Ser-Phe and Trp-Leu, were found in the cytochrome P450 CYP6C and CYP9F genes of the B and Q biotypes. Bioassay results also revealed that both the B and Q biotypes have about 12-47 times more resistance to acephate, beta- cypermethrin, methomyl, and 5-7 times more resistance to imidacloprid insecticide than Cv population. Our results provide a molecular approach for better understanding and monitoring the pesticide resistances of invasive and native B. tabaei populations in China.展开更多
Background:Fuchs endothelial corneal dystrophy is a hereditary disease and the most frequent cause of corneal transplantation in the worldwide.Its main clinical signs are an accelerated decrease in the number of endot...Background:Fuchs endothelial corneal dystrophy is a hereditary disease and the most frequent cause of corneal transplantation in the worldwide.Its main clinical signs are an accelerated decrease in the number of endothelial cells,thickening of Descemet’s membrane and formation of guttae in the extracellular matrix.The cornea’s ability to maintain stromal dehydration is impaired,causing painful epithelial bullae and loss of vision at the point when the amount of corneal endothelial cells cannot be compensated.At present,apart from corneal transplantation,there is no other effective treatment that prevents blindness.Main text:In this review,we first summarized the mutations of COL8A2,TCF4,TCF8,SLC4A11 and AGBL1 genes in Fuchs endothelial corneal dystrophy.The molecular mechanisms associated with Fuchs endothelial corneal dystrophy,such as endoplasmic reticulum stress and unfolded protein response pathway,oxidative stress,mitochondrial dysregulation pathway,apoptosis pathway,mitophagy,epithelial-mesenchymal transition pathway,RNA toxicity and repeat-associated non-ATG translation,and other pathogenesis,were then explored.Finally,we discussed several potential treatments related to the pathogenesis of Fuchs endothelial corneal dystrophy,which may be the focus of future research.Conclusions:The pathogenesis of Fuchs endothelial corneal dystrophy is very complicated.Currently,corneal transplantation is an important method in the treatment of Fuchs endothelial corneal dystrophy.It is necessary to continuously explore the pathogenesis of Fuchs endothelial corneal dystrophy and establish the scientific foundations for the development of next-generation corneal therapeutics.展开更多
Monogenic diabetes is caused by one or even more genetic variations, which maybe uncommon yet have a significant influence and cause diabetes at an early age.Monogenic diabetes affects 1 to 5% of children, and early d...Monogenic diabetes is caused by one or even more genetic variations, which maybe uncommon yet have a significant influence and cause diabetes at an early age.Monogenic diabetes affects 1 to 5% of children, and early detection and geneticallyfocused treatment of neonatal diabetes and maturity-onset diabetes of theyoung can significantly improve long-term health and well-being. The etiology ofmonogenic diabetes in childhood is primarily attributed to genetic variationsaffecting the regulatory genes responsible for beta-cell activity. In rare instances,mutations leading to severe insulin resistance can also result in the developmentof diabetes. Individuals diagnosed with specific types of monogenic diabetes,which are commonly found, can transition from insulin therapy to sulfonylureas,provided they maintain consistent regulation of their blood glucose levels.Scientists have successfully devised materials and methodologies to distinguishindividuals with type 1 or 2 diabetes from those more prone to monogenicdiabetes. Genetic screening with appropriate findings and interpretations isessential to establish a prognosis and to guide the choice of therapies andmanagement of these interrelated ailments. This review aims to design a comprehensiveliterature summarizing genetic insights into monogenetic diabetes inchildren and adolescents as well as summarizing their diagnosis and management.展开更多
Uveal melanoma(UM)is the most common primary intraocular cancer in adults.The incidence in Europe and the United States is 6-7 per million population per year.Although most primary UMs can be successfully treated and ...Uveal melanoma(UM)is the most common primary intraocular cancer in adults.The incidence in Europe and the United States is 6-7 per million population per year.Although most primary UMs can be successfully treated and locally controlled by irradiation therapy or local tumor resection,up to 50%of UM patients develop metastases that usually involve the liver and are fatal within 1 year.To date,chemotherapy and targeted treatments only obtain minimal responses in patients with metastatic UM,which is still characterized by poor prognosis.No standard therapeutic approaches for its prevention or treatment have been established.The application of immunotherapy agents,such as immune checkpoint inhibitors that are effective in cutaneous melanoma,has shown limited effects in the treatment of ocular disease.This is due to UM’s distinct genetics,natural history,and complex interaction with the immune system.Unlike cutaneous melanomas characterized mainly by BRAF or NRAS mutations,UMs are usually triggered by a mutation in GNAQ or GNA11.As a result,more effective immunotherapeutic approaches,such as cancer vaccines,adoptive cell transfer,and other new molecules are currently being studied.In this review,we examine novel immunotherapeutic strategies in clinical and preclinical studies and highlight the latest insight in immunotherapy and the development of tailored treatment of UM.展开更多
Living objects have complex internal and external interactions. The complexity is regulated and controlled by homeostasis, which is the balance of multiple opposing influences. The environmental effects finally guide ...Living objects have complex internal and external interactions. The complexity is regulated and controlled by homeostasis, which is the balance of multiple opposing influences. The environmental effects finally guide the self-organized structure. The living systems are open, dynamic structures performing random, stationary, stochastic, self-organizing processes. The self-organizing procedure is defined by the spatial-temporal fractal structure, which is self-similar both in space and time. The system’s complexity appears in its energetics, which tries the most efficient use of the available energies;for that, it organizes various well-connected networks. The controller of environmental relations is the Darwinian selection on a long-time scale. The energetics optimize the healthy processes tuned to the highest efficacy and minimal loss (minimalization of the entropy production). The organism is built up by morphogenetic rules and develops various networks from the genetic level to the organism. The networks have intensive crosstalk and form a balance in the Nash equilibrium, which is the homeostatic state in healthy conditions. Homeostasis may be described as a Nash equilibrium, which ensures energy distribution in a “democratic” way regarding the functions of the parts in the complete system. Cancer radically changes the network system in the organism. Cancer is a network disease. Deviation from healthy networking appears at every level, from genetic (molecular) to cells, tissues, organs, and organisms. The strong proliferation of malignant tissue is the origin of most of the life-threatening processes. The weak side of cancer development is the change of complex information networking in the system, being vulnerable to immune attacks. Cancer cells are masters of adaptation and evade immune surveillance. This hiding process can be broken by electromagnetic nonionizing radiation, for which the malignant structure has no adaptation strategy. Our objective is to review the different sides of living complexity and use the knowledge to fight against cancer.展开更多
Familial hypercholesterolemia(FH)is characterized by elevated low-density lipoprotein cholesterol levels due to genetic mutations,presenting with xanthomas,corneal arch,and severe cardiovascular diseases.Early identif...Familial hypercholesterolemia(FH)is characterized by elevated low-density lipoprotein cholesterol levels due to genetic mutations,presenting with xanthomas,corneal arch,and severe cardiovascular diseases.Early identification,diagnosis,and treatment are crucial to prevent severe complications like acute myocardial infarction.Statins are the primary treatment,supplemented by Ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors,though their effectiveness can be limited in severe cases.Over 90%of FH cases remain undiagnosed,and current treatments are often inadequate,underscoring the need for improved diagnostic and management systems.Future strategies include advancements in gene testing,precision medicine,and novel drugs,along with gene therapy approaches like AAV-mediated gene therapy and clustered regularly interspaced short palindromic repeats.Lifestyle modifications,including health education,dietary control,and regular exercise,are essential for managing FH and preventing related diseases.Research into FH-related gene mutations,especially LDLR,is critical for accurate diagnosis and effective treatment.展开更多
The association between genetic syndromes and odontogenic tumors encompasses several entities,reflecting the intricate interplay between genetic factors and the development of these lesions.The present study aimed to ...The association between genetic syndromes and odontogenic tumors encompasses several entities,reflecting the intricate interplay between genetic factors and the development of these lesions.The present study aimed to comprehensively investigate the associations between genetic syndromes and odontogenic tumors.We delineated the diverse spectrum of syndromic connections,including key syndromes such as Gardner syndrome,Gorlin syndrome,Schimmelpenning syndrome,and others.Our findings underscore the clinical significance of recognizing odontogenic tumors associated with genetic syndromes as diagnostic indicators for early intervention.We advocate for multidisciplinary collaboration among clinicians,geneticists,and researchers to deepen our understanding of the underlying mechanisms driving these syndromic associations.In light of this,our study contributes to the growing body of knowledge in dentistry and medical genetics,offering insights that may inform clinical practice and enhance patient care for individuals affected by genetic syndromes and odontogenic tumors.展开更多
BACKGROUND We analyzed the main features of an infant diagnosed with temporary neonatal cyanosis in order to strengthen our understanding of the disease.CASE SUMMARY We report a patient diagnosed with temporary neonat...BACKGROUND We analyzed the main features of an infant diagnosed with temporary neonatal cyanosis in order to strengthen our understanding of the disease.CASE SUMMARY We report a patient diagnosed with temporary neonatal cyanosis.The main clinical characteristics,gene mutation and treatment are discussed and a review of related literature was conducted.The neonate aged 1 d and 5 h was admitted to hospital due to cyanosis after birth.The main clinical manifestation was cyanosis,which was not improved by auxiliary ventilation and the patient showed no obvious shortness of breath or methemoglobinemia.Gene mutation analysis showed a heterozygous c.190C>T mutation in the HBG2 gene associated with transient neonatal cyanosis,which was derived from his mother.Symptomatic supportive treatment was given for 2 mo.The neonate was discharged and gradually improved with oral administration of vitamin C and vitamin B2 for 2 wk.CONCLUSION There is no special treatment for temporary neonatal cyanosis caused by heterozygous mutation of the HBG2 gene.展开更多
AIM：To investigate the genetic mutations that are associated the hereditary autosomal dominant cataract in a Chinese family.METHODS：A Chinese family consisting of 20 cataract patients（including 9 male and 11 female...AIM：To investigate the genetic mutations that are associated the hereditary autosomal dominant cataract in a Chinese family.METHODS：A Chinese family consisting of 20 cataract patients（including 9 male and 11 female） and 2 unaffected individuals from 5 generations were diagnosed to be a typical autosomal dominant cataract pedigree. Genomic DNA samples were extracted from the peripheral blood cells of the participants in this pedigree. Exon sequence was used for genetic mutation screening. In silico analysis was used to study the structure characteristics of connexin 46（CX46） mutant. Immunoblotting was conduceted for testing the expression of CX46.RESULTS：To determine the involved genetic mutations, 11 well-known cataract-associated genes（cryaa, cryab, crybb1, crybb2, crygc, crygd, Gja3, Gja8, Hsf4, Mip and Pitx3） were chosen for genetic mutation test by using exon sequencing. A novel cytosine insertion at position 1195 of CX46 c DNA（c.1194_1195ins C） was found in the samples of 5 tested cataract patients but not in the unaffected 2 individuals nor in normal controls, which resulted in 30 amino acids more extension in CX46Cterminus（cx46fs400） compared with the wild-type CX46. In silico protein structure analysis indicated that the mutant showed distinctive hydrophobicity and protein secondary structure compared with the wild-type CX46. The immunoblot results revealed that CX46 protein, which expressed in the aging cataract lens tissues, was absence in the proband lens. In contrast, CX50, alpha A-crystallin and alphaB-crystallin expressed equally in both proband and aging cataract tissues. Those results revealed that the cx46fs400 mutation could impair CX46 protein expression. CONCLUSION：The insertion of cytosine at position 1195 of CX46 cD NA is a novel mutation site that is associated with the autosomal dominant cataracts in this Chinese family. The C-terminal frameshift mutation is involved in regulating CX46 protein expression.展开更多
The rare disease of chronic infantile neurological cutaneous and articular(CINCA)syndrome,is caused by the over-secretion of interleukin(IL)-1βdue to a gain-of-function NLRP3 gene mutation in the autosomal chromosome...The rare disease of chronic infantile neurological cutaneous and articular(CINCA)syndrome,is caused by the over-secretion of interleukin(IL)-1βdue to a gain-of-function NLRP3 gene mutation in the autosomal chromosome which often involves in eyes.In this report,we studied a 9-year-old girl with CINCA.The eyes were also involved and presented bilateral papilledema.Genetic testing revealed that the symptoms were caused by a novel gene mutation site(c.913G>A,p.D305N)in conservative domain exon-3 of NLRP3 which is gain-function gene of CINCA.The patient had the characteristic facial features,frontal fossa and saddle nose,manifested the generalized urticaria-like skin rash at two weeks after birth,periodic fever 6 months after birth,sensorineural deafness at 7 years old,and bilateral papilledema,aseptic meningitis and knee arthropathy at 9 years old.White cell counts,C-reactive protein increased and intracranial pressure raised to 300 mmH2O.The meningeal thickening enhanced by gadolinium in magnetic resonance imaging(MRI).Based on clinical features and genetic test,the girl was diagnosed bilateral papilledema secondary to CINCA and administered prednisone and lowered intracranial pressure medicine to resolve symptoms.With 3-year follow-up,patient had no inflammatory flare-up with visual acuity improvement.The finding of novel genetic mutation site(p.D305N)in NLRP3 gene expanded genotype spectrum associated with CINCA.This case also expanded the cause spectrum of papilledema and it highlighted systemic disease history for patients with bilateral papilledema.展开更多
The triple A or AIIgrove＇s syndrome is an autosomal recessive disorder characterized by the triad of achalasia cardia, alacrima and ACTH resistant adrenocortical insufficiency. Mutations of the Achalasia-Addisonianis...The triple A or AIIgrove＇s syndrome is an autosomal recessive disorder characterized by the triad of achalasia cardia, alacrima and ACTH resistant adrenocortical insufficiency. Mutations of the Achalasia-AddisonianismAlacrima-Syndrome （AAAS） gene on chromosome 12q13 are associated with this syndrome. We report an Indian family where two siblings were homozygous for a known mutation of the AAAS gene and presented with the classical triad of symptoms. The mother and the brother were heterozygous and asymptomatic. The affected siblings had iron deficiency anemia and the younger sister had pes cavus and palmoplantar keratosis. Neurological symptoms were absent in both affected children. Recognition of this syndrome can lead to early treatment of adrenal insufficency and genetic counselling.展开更多
Meanwhile the outbreak of the Covid-19 since December, 2019 in China, it has killed more than a hundred thousand of people of all ages and sex across the globe in a short span of time. On the bases of this study the n...Meanwhile the outbreak of the Covid-19 since December, 2019 in China, it has killed more than a hundred thousand of people of all ages and sex across the globe in a short span of time. On the bases of this study the nearest family member of the virus and its receptor binding domain of S protein including its model structure and function of its active sites were naked through Multiple Sequence Alignment, modelling and molecular docking software accordingly its repository genome databases. The virus was genetically associated and molecular evolutionary related with (<em>RaTG</em>13) and it scores 96.12% homology with 99% query coverage followed by <em>bat-SL-CoVZC</em>45 and<em> bat-SL-CoVZXC</em>21 notch 89.12% and 88.65% respectively. However, SARS and MERS corona type virus those outbreak earlier respectively less likely family members of 2019-nCoV. Though the virus has a close genetic association with those previous SARS coronaviruses, and certainly the spike protein used as a binding receptor to fight against human receptor protein of ACE 2, but on the basis of FRODOC and HDOCK server analysis multi favorable active sites of S protein was discovered such GLN493 shown as a finest key in both model and possessed a unique traits on it resulting unexpected rate of transmission and number of people died while compared to the previous one. TYR500, ASN501, GLN498 and others residues preferably contemplate site also. In particular, the diversity of the virus in the world may be due to the genome structure of the virus and S gene changed over the time, across the world against to host of human genetic diversity, which may be more robust, and may be a new and unique feature. This is because it is characterized close to contact with distance divergence between wild type novel coronavirus which was risen from China against to the genomes from Lebanon, India, Italy, and USA and so on. Thus, the World Health Organization and its researchers should focus on immunologic research and effective drug and vaccine development that will help to address the epidemiology of the virus, which can provide a long-term solution.展开更多
Gastric cancer is one of the leading causes of cancer-related deaths worldwide. Among which, about 1%–3% of gastric cancer patients were characterized by inherited gastric cancer predisposition syndromes, knowing as ...Gastric cancer is one of the leading causes of cancer-related deaths worldwide. Among which, about 1%–3% of gastric cancer patients were characterized by inherited gastric cancer predisposition syndromes, knowing as hereditary diffuse gastric cancer（HDGC）. Studies reported that CDH1 germline mutations are the main cause of HDGC. With the help of rapid development of genetic testing technologies and data analysis tools, more and more researchers focus on seeking candidate susceptibility genes for hereditary cancer syndromes. In addition, National Comprehensive Cancer Network（NCCN） guidelines recommend that the patients of HDGC carrying CDH1 mutations should undergo prophylactic gastrectomy or routine endoscopic surveillances. Therefore, genetic counseling plays a key role in helping individuals with pathogenic mutations make appropriate risk management plans. Moreover, experienced and professional genetic counselors as well as a systematic multidisciplinary team（MDT） are also required to facilitate the development of genetic counseling and benefit pathogenic mutation carriers who are in need of regular and standardized risk management solutions. In this review, we provided an overview about the germline mutations of several genes identified in HDGC, suggesting that these genes may potentially act as susceptibility genes for this malignant cancer syndrome. Furthermore, we introduced information for prevention, diagnosis and risk management of HDGC. Investigations on key factors that may have effect on risk management decision-making and genetic data collection of more cancer syndrome family pedigrees are required for the development of HDGC therapeutic strategies.展开更多
Presenilin(Psn)protein is associated with organismal aging.Mutations in the Psn gene may lead to Alzheimer’s disease(AD),dilated cardiomyopathy(DCM),and many age-dependent degenerative diseases.These diseases serious...Presenilin(Psn)protein is associated with organismal aging.Mutations in the Psn gene may lead to Alzheimer’s disease(AD),dilated cardiomyopathy(DCM),and many age-dependent degenerative diseases.These diseases seriously affect the quality of life and longevity of the population and place a huge burden on health care and economic systems around the world.Humans have two types of Psn,presenilin-1(PSEN1)and presenilin-2(PSEN2).Mutations in the genes encoding PSEN1,PSEN2,and amyloid precursor protein(APP)have been identified as the major genetic causes of AD.Psn is a complex gene strongly influenced by genetic and environmental factors.The effects of exercise,training,and a high-fat diet on the Psn gene expressed in the heart and its related pathways are not fully understood.Fortunately,relevant aspects of the mutational effects on Psn can be studied experimentally in easily handled animal models,including Drosophila,mice,and other animals,all of which share orthologous genes of Psn with humans.Many previous studies have linked aging,exercise training,and a high-fat diet to the Psn gene.This review discusses the interrelationship between aging,exercise training,and a high-fat diet on the Psn gene and its associated disease,AD.The aim is to understand the adverse effects of Psn gene mutations on the body and the diseases caused by AD,find ways to alleviate the adverse effects and provide new directions for the improvement of treatment strategies for diseases caused by Psn gene mutations.展开更多
基金Shanghai Science and Technology Commission“R&D Public Service Platform and Institutional Capacity Improvement Project”,Grant/Award Number:21DZ2291300National Science and Technology Major Project,Grant/Award Number:2017ZX10304402-001-006 and 2017ZX10304402-001-012Start-on Funding from Shanghai Public Health Clinical Center,Grant/Award Number:KY-GW-2019-11,KYGW-2019-19 and KY-GW-2021-39。
文摘Background:Bitter taste receptors(Tas2rs)are generally considered to sense various bitter compounds to escape the intake of toxic substances.Bitter taste receptors have been found to widely express in extraoral tissues and have important physiological functions outside the gustatory system in vivo.Methods:To investigate the physiological functions of the bitter taste receptor cluster Tas2r106/Tas2r104/Tas2r105/Tas2r114 in lingual and extraoral tissues,multiple Tas2rs mutant mice and Gnat3 were produced using CRISPR/Cas9 gene-editing technique.A mixture containing Cas9 and sgRNA mRNAs for Tas2rs and Gnat3 gene was microinjected into the cytoplasm of the zygotes.Then,T7EN1 assays and sequencing were used to screen genetic mutation at the target sites in founder mice.Quantitative real-time polymerase chain reaction(qRT-PCR)and immunostaining were used to study the expression level of taste signaling cascade and bitter taste receptor in taste buds.Perception to taste substance was also studied using twobottle preference tests.Results:We successfully produced several Tas2rs and Gnat3 mutant mice using the CRISPR/Cas9 technique.Immunostaining results showed that the expression of GNAT3 and PLCB2 was not altered in Tas2rs mutant mice.But qRT-PCR results revealed the changed expression profile of m Tas2rs gene in taste buds of these mutant mice.With two-bottle preference tests,these mutant mice eliminate responses to cycloheximide due to genetic mutation of Tas2r105.In addition,these mutant mice showed a loss of taste perception to quinine dihydrochloride,denatonium benzoate,and cucurbitacin B(CuB).Gnat3-mediated taste receptor and its signal pathway contribute to CuB perception.Conclusions:These findings implied that these mutant mice would be a valuable means to understand the biological functions of TAS2Rs in extraoral tissues and investigate bitter compound-induced responses mediated by these TAS2Rs in many extraoral tissues.
文摘BACKGROUND Pancreatic cancer(PC)is one of the deadliest malignancies with an alarming mortality rate.Despite significant advancement in diagnostics and therapeutics,early diagnosis remains elusive causing poor prognosis,marred by mutations and epigenetic modifications in key genes which contribute to disease progression.AIM To evaluate the various biological tumor markers collectively for early diagnosis which could act as prognostic biomarkers and helps in future therapeutics of PC in Kashmir valley.METHODS A total of 50 confirmed PC cases were included in the study to evaluate the levels of carbohydrate antigen 19-9(CA 19-9),tissue polypeptide specific antigen(TPS),carcinoembryonic antigen(CEA),vascular endothelial growth factor-A(VEGF-A),and epidermal growth factor receptor(EGFR).Mutational analysis was performed to evaluate the mutations in Kirsten rat sarcoma(KRAS),Breast cancer type 2(BRCA-2),and deleted in pancreatic cancer-4(DPC-4)genes.However,epigenetic modifications(methylation of CpG islands)were performed in the promoter regions of cyclin-dependent kinase inhibitor 2A(p16;CDKN2A),MutL homolog 1(hMLH1),and Ras association domain-containing protein 1(RASSF1A)genes.RESULTS We found significantly elevated levels of biological markers CA 19-9(P≤0.05),TPS(P≤0.05),CEA(P≤0.001),and VEGF(P≤0.001).Molecular genetic analysis revealed that KRAS gene mutation is predominant in codon 12(16 subjects,P≤0.05),and 13(12 subjects,P≤0.05).However,we did not find a mutation in DPC-4(1203G>T)and BRCA-2(617delT)genes.Furthermore,epigenetic modification revealed that CpG methylation in 21(P≤0.05)and 4 subjects in the promoter regions of the p16 and hMLH1 gene,respectively.CONCLUSION In conclusion,CA 19-9,TPS,CEA,and VEGF levels were significantly elevated and collectively have potential as diagnostic and prognostic markers in PC.Global data of mutation in the KRAS gene commonly in codon 12 and rare in codon 13 could augment the predisposition towards PC.Additionally,methylation of the p16 gene could also modulate transcription of genes thereby increasing the predisposition and susceptibility towards PC.
基金Supported by National Natural Science Foundation of China,No.81703017The Science and Technology Projects of Guangzhou,China,No.201804010080.
文摘BACKGROUND Polyostotic fibrous dysplasia(PFD)is an uncommon developmental bone disease in which normal bone and marrow are replaced by pseudotumoral tissue.The etiology of PFD is unclear,but it is generally thought to be caused by sporadic,post-zygotic mutations in the GNAS gene.Herein,we report the case of a young female with bone pain and lesions consistent with PFD,unique physical findings,and gene mutations.CASE SUMMARY A 27-year-old female presented with unbearable bone pain in her left foot for 4 years.Multiple bone lesions were detected by radiographic examinations,and a diagnosis of PFD was made after a biopsy of her left calcaneus with symptoms including pre-axial polydactyly on her left hand and severe ophthalmological problems such as high myopia,vitreous opacity,and choroidal atrophy.Her serum cortisol level was high,consistent with Cushing syndrome.Due to consanguineous marriage of her grandparents,boosted whole exome screening was performed to identify gene mutations.The results revealed mutations in HSPG2 and RIMS1,which may be contributing factors to her unique findings.CONCLUSION The unique findings in this patient with PFD may be related to mutations in the HSPG2 and RIMS1 genes.
基金supported by the National Natural Science Foundation of China,No.U21A20347(to CZ)the National Key Research and Development Program of China,No.2022YFC2704801(to CZ)+1 种基金the Henan Key Laboratory of Population Defects Prevention,No.ZD202103(to YX)the Department of Science and Technology of Henan Province of China,No.212102310221(to YX)。
文摘Ce rebral palsy is a diagnostic term utilized to describe a group of permanent disorders affecting movement and posture.Patients with cerebral palsy are often only capable of limited activity,resulting from non-progressive disturbances in the fetal or neonatal brain.These disturbances severely impact the child’s daily life and impose a substantial economic burden on the family.Although cerebral palsy encompasses various brain injuries leading to similar clinical outcomes,the unde rstanding of its etiological pathways remains incomplete owing to its complexity and heterogeneity.This review aims to summarize the current knowledge on the genetic factors influencing cerebral palsy development.It is now widely acknowledged that genetic mutations and alterations play a pivotal role in cerebral palsy development,which can be further influenced by environmental fa ctors.Des pite continuous research endeavors,the underlying fa ctors contributing to cerebral palsy remain are still elusive.However,significant progress has been made in genetic research that has markedly enhanced our comprehension of the genetic factors underlying cerebral palsy development.Moreove r,these genetic factors have been categorized based on the identified gene mutations in patients through clinical genotyping,including thrombosis,angiogenesis,mitochondrial and oxidative phosphorylation function,neuronal migration,and cellular autophagy.Furthermore,exploring targeted genotypes holds potential for precision treatment.In conclusion,advancements in genetic research have substantially improved our understanding of the genetic causes underlying cerebral palsy.These breakthroughs have the potential to pave the way for new treatments and therapies,consequently shaping the future of cerebral palsy research and its clinical management.The investigation of cerebral palsy genetics holds the potential to significantly advance treatments and management strategies.By elucidating the underlying cellular mechanisms,we can develop to rgeted interventions to optimize outcomes.A continued collaboration between researchers and clinicians is imperative to comprehensively unravel the intricate genetic etiology of cerebral palsy.
文摘Monogenic diabetes is caused by one or even more genetic variations,which may be uncommon yet have a significant influence and cause diabetes at an early age.Monogenic diabetes affects 1%to 5%of children,and early detection and genetically focused treatment of neonatal diabetes and maturity-onset diabetes of the young can significantly improve long-term health and well-being.The etiology of monogenic diabetes in childhood is primarily attributed to genetic variations affecting the regulatory genes responsible for beta-cell activity.In rare instances,mutations leading to severe insulin resistance can also result in the development of diabetes.Individuals diagnosed with specific types of monogenic diabetes,which are commonly found,can transition from insulin therapy to sulfonylureas,provided they maintain consistent regulation of their blood glucose levels.Scientists have successfully devised materials and methodologies to distinguish individuals with type 1 or 2 diabetes from those more prone to monogenic diabetes.Genetic screening with appropriate findings and interpretations is essential to establish a prognosis and to guide the choice of therapies and management of these interrelated ailments.This review aims to design a comprehensive literature summarizing genetic insights into monogenetic diabetes in children and adolescents as well as summarizing their diagnosis and management.
基金Supported by Natural Science Foundation of Shanghai,No.17ZR1431400National Key R and D Program of China,No.2017YFA0103902.
文摘Sotos syndrome is characterized by overgrowth features and is caused by alterations in the nuclear receptor binding SET domain protein 1 gene.Attentiondeficit/hyperactivity disorder(ADHD)is considered a neurodevelopment and psychiatric disorder in childhood.Genetic characteristics and clinical presentation could play an important role in the diagnosis of Sotos syndrome and ADHD.Magnetic resonance imaging(MRI)has been used to assess medical images in Sotos syndrome and ADHD.The images process is considered to display in MRI while wavelet fusion has been used to integrate distinct images for achieving more complete information in single image in this editorial.In the future,genetic mechanisms and artificial intelligence related to medical images could be used in the clinical diagnosis of Sotos syndrome and ADHD.
文摘Bemisia tabaci （Gennadius） is a species complex, and its two most damaging biotypes B and Q are globally distributed pests. Despite increasing biological and economic impacts, little is known about the evolutionary mechanisms that favor their competition with native populations. Here, we investigated the genetic mutations in the P450 gene of the invasive B, Q biotypes and the native Cv population. Four mutations associated with chemical resistance, Pro-Leu, Ala-Ser, Ser-Phe and Trp-Leu, were found in the cytochrome P450 CYP6C and CYP9F genes of the B and Q biotypes. Bioassay results also revealed that both the B and Q biotypes have about 12-47 times more resistance to acephate, beta- cypermethrin, methomyl, and 5-7 times more resistance to imidacloprid insecticide than Cv population. Our results provide a molecular approach for better understanding and monitoring the pesticide resistances of invasive and native B. tabaei populations in China.
基金supported by the Heilongjiang Postdoctoral Fund(Grant No.LBH-Z18185)the Heilongjiang Provincial Colleges and Universities Basic Scientific Research Fund(Grant No.2018-KYYWF-0484).
文摘Background:Fuchs endothelial corneal dystrophy is a hereditary disease and the most frequent cause of corneal transplantation in the worldwide.Its main clinical signs are an accelerated decrease in the number of endothelial cells,thickening of Descemet’s membrane and formation of guttae in the extracellular matrix.The cornea’s ability to maintain stromal dehydration is impaired,causing painful epithelial bullae and loss of vision at the point when the amount of corneal endothelial cells cannot be compensated.At present,apart from corneal transplantation,there is no other effective treatment that prevents blindness.Main text:In this review,we first summarized the mutations of COL8A2,TCF4,TCF8,SLC4A11 and AGBL1 genes in Fuchs endothelial corneal dystrophy.The molecular mechanisms associated with Fuchs endothelial corneal dystrophy,such as endoplasmic reticulum stress and unfolded protein response pathway,oxidative stress,mitochondrial dysregulation pathway,apoptosis pathway,mitophagy,epithelial-mesenchymal transition pathway,RNA toxicity and repeat-associated non-ATG translation,and other pathogenesis,were then explored.Finally,we discussed several potential treatments related to the pathogenesis of Fuchs endothelial corneal dystrophy,which may be the focus of future research.Conclusions:The pathogenesis of Fuchs endothelial corneal dystrophy is very complicated.Currently,corneal transplantation is an important method in the treatment of Fuchs endothelial corneal dystrophy.It is necessary to continuously explore the pathogenesis of Fuchs endothelial corneal dystrophy and establish the scientific foundations for the development of next-generation corneal therapeutics.
文摘Monogenic diabetes is caused by one or even more genetic variations, which maybe uncommon yet have a significant influence and cause diabetes at an early age.Monogenic diabetes affects 1 to 5% of children, and early detection and geneticallyfocused treatment of neonatal diabetes and maturity-onset diabetes of theyoung can significantly improve long-term health and well-being. The etiology ofmonogenic diabetes in childhood is primarily attributed to genetic variationsaffecting the regulatory genes responsible for beta-cell activity. In rare instances,mutations leading to severe insulin resistance can also result in the developmentof diabetes. Individuals diagnosed with specific types of monogenic diabetes,which are commonly found, can transition from insulin therapy to sulfonylureas,provided they maintain consistent regulation of their blood glucose levels.Scientists have successfully devised materials and methodologies to distinguishindividuals with type 1 or 2 diabetes from those more prone to monogenicdiabetes. Genetic screening with appropriate findings and interpretations isessential to establish a prognosis and to guide the choice of therapies andmanagement of these interrelated ailments. This review aims to design a comprehensiveliterature summarizing genetic insights into monogenetic diabetes inchildren and adolescents as well as summarizing their diagnosis and management.
文摘Uveal melanoma(UM)is the most common primary intraocular cancer in adults.The incidence in Europe and the United States is 6-7 per million population per year.Although most primary UMs can be successfully treated and locally controlled by irradiation therapy or local tumor resection,up to 50%of UM patients develop metastases that usually involve the liver and are fatal within 1 year.To date,chemotherapy and targeted treatments only obtain minimal responses in patients with metastatic UM,which is still characterized by poor prognosis.No standard therapeutic approaches for its prevention or treatment have been established.The application of immunotherapy agents,such as immune checkpoint inhibitors that are effective in cutaneous melanoma,has shown limited effects in the treatment of ocular disease.This is due to UM’s distinct genetics,natural history,and complex interaction with the immune system.Unlike cutaneous melanomas characterized mainly by BRAF or NRAS mutations,UMs are usually triggered by a mutation in GNAQ or GNA11.As a result,more effective immunotherapeutic approaches,such as cancer vaccines,adoptive cell transfer,and other new molecules are currently being studied.In this review,we examine novel immunotherapeutic strategies in clinical and preclinical studies and highlight the latest insight in immunotherapy and the development of tailored treatment of UM.
文摘Living objects have complex internal and external interactions. The complexity is regulated and controlled by homeostasis, which is the balance of multiple opposing influences. The environmental effects finally guide the self-organized structure. The living systems are open, dynamic structures performing random, stationary, stochastic, self-organizing processes. The self-organizing procedure is defined by the spatial-temporal fractal structure, which is self-similar both in space and time. The system’s complexity appears in its energetics, which tries the most efficient use of the available energies;for that, it organizes various well-connected networks. The controller of environmental relations is the Darwinian selection on a long-time scale. The energetics optimize the healthy processes tuned to the highest efficacy and minimal loss (minimalization of the entropy production). The organism is built up by morphogenetic rules and develops various networks from the genetic level to the organism. The networks have intensive crosstalk and form a balance in the Nash equilibrium, which is the homeostatic state in healthy conditions. Homeostasis may be described as a Nash equilibrium, which ensures energy distribution in a “democratic” way regarding the functions of the parts in the complete system. Cancer radically changes the network system in the organism. Cancer is a network disease. Deviation from healthy networking appears at every level, from genetic (molecular) to cells, tissues, organs, and organisms. The strong proliferation of malignant tissue is the origin of most of the life-threatening processes. The weak side of cancer development is the change of complex information networking in the system, being vulnerable to immune attacks. Cancer cells are masters of adaptation and evade immune surveillance. This hiding process can be broken by electromagnetic nonionizing radiation, for which the malignant structure has no adaptation strategy. Our objective is to review the different sides of living complexity and use the knowledge to fight against cancer.
基金Supported by National Key Research and Development Program of China,No.2022YFE0209900.
文摘Familial hypercholesterolemia(FH)is characterized by elevated low-density lipoprotein cholesterol levels due to genetic mutations,presenting with xanthomas,corneal arch,and severe cardiovascular diseases.Early identification,diagnosis,and treatment are crucial to prevent severe complications like acute myocardial infarction.Statins are the primary treatment,supplemented by Ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors,though their effectiveness can be limited in severe cases.Over 90%of FH cases remain undiagnosed,and current treatments are often inadequate,underscoring the need for improved diagnostic and management systems.Future strategies include advancements in gene testing,precision medicine,and novel drugs,along with gene therapy approaches like AAV-mediated gene therapy and clustered regularly interspaced short palindromic repeats.Lifestyle modifications,including health education,dietary control,and regular exercise,are essential for managing FH and preventing related diseases.Research into FH-related gene mutations,especially LDLR,is critical for accurate diagnosis and effective treatment.
文摘The association between genetic syndromes and odontogenic tumors encompasses several entities,reflecting the intricate interplay between genetic factors and the development of these lesions.The present study aimed to comprehensively investigate the associations between genetic syndromes and odontogenic tumors.We delineated the diverse spectrum of syndromic connections,including key syndromes such as Gardner syndrome,Gorlin syndrome,Schimmelpenning syndrome,and others.Our findings underscore the clinical significance of recognizing odontogenic tumors associated with genetic syndromes as diagnostic indicators for early intervention.We advocate for multidisciplinary collaboration among clinicians,geneticists,and researchers to deepen our understanding of the underlying mechanisms driving these syndromic associations.In light of this,our study contributes to the growing body of knowledge in dentistry and medical genetics,offering insights that may inform clinical practice and enhance patient care for individuals affected by genetic syndromes and odontogenic tumors.
基金Supported by National Natural Science Foundation of China,No.81771626
文摘BACKGROUND We analyzed the main features of an infant diagnosed with temporary neonatal cyanosis in order to strengthen our understanding of the disease.CASE SUMMARY We report a patient diagnosed with temporary neonatal cyanosis.The main clinical characteristics,gene mutation and treatment are discussed and a review of related literature was conducted.The neonate aged 1 d and 5 h was admitted to hospital due to cyanosis after birth.The main clinical manifestation was cyanosis,which was not improved by auxiliary ventilation and the patient showed no obvious shortness of breath or methemoglobinemia.Gene mutation analysis showed a heterozygous c.190C>T mutation in the HBG2 gene associated with transient neonatal cyanosis,which was derived from his mother.Symptomatic supportive treatment was given for 2 mo.The neonate was discharged and gradually improved with oral administration of vitamin C and vitamin B2 for 2 wk.CONCLUSION There is no special treatment for temporary neonatal cyanosis caused by heterozygous mutation of the HBG2 gene.
基金Supported by the National Natural Science Foundation of China(No.81570825No.81400387+1 种基金No.U1404810)Henan Education Committee Foundations for Talent Innovative Technology(No.14IRTSTHN019)
文摘AIM：To investigate the genetic mutations that are associated the hereditary autosomal dominant cataract in a Chinese family.METHODS：A Chinese family consisting of 20 cataract patients（including 9 male and 11 female） and 2 unaffected individuals from 5 generations were diagnosed to be a typical autosomal dominant cataract pedigree. Genomic DNA samples were extracted from the peripheral blood cells of the participants in this pedigree. Exon sequence was used for genetic mutation screening. In silico analysis was used to study the structure characteristics of connexin 46（CX46） mutant. Immunoblotting was conduceted for testing the expression of CX46.RESULTS：To determine the involved genetic mutations, 11 well-known cataract-associated genes（cryaa, cryab, crybb1, crybb2, crygc, crygd, Gja3, Gja8, Hsf4, Mip and Pitx3） were chosen for genetic mutation test by using exon sequencing. A novel cytosine insertion at position 1195 of CX46 c DNA（c.1194_1195ins C） was found in the samples of 5 tested cataract patients but not in the unaffected 2 individuals nor in normal controls, which resulted in 30 amino acids more extension in CX46Cterminus（cx46fs400） compared with the wild-type CX46. In silico protein structure analysis indicated that the mutant showed distinctive hydrophobicity and protein secondary structure compared with the wild-type CX46. The immunoblot results revealed that CX46 protein, which expressed in the aging cataract lens tissues, was absence in the proband lens. In contrast, CX50, alpha A-crystallin and alphaB-crystallin expressed equally in both proband and aging cataract tissues. Those results revealed that the cx46fs400 mutation could impair CX46 protein expression. CONCLUSION：The insertion of cytosine at position 1195 of CX46 cD NA is a novel mutation site that is associated with the autosomal dominant cataracts in this Chinese family. The C-terminal frameshift mutation is involved in regulating CX46 protein expression.
文摘The rare disease of chronic infantile neurological cutaneous and articular(CINCA)syndrome,is caused by the over-secretion of interleukin(IL)-1βdue to a gain-of-function NLRP3 gene mutation in the autosomal chromosome which often involves in eyes.In this report,we studied a 9-year-old girl with CINCA.The eyes were also involved and presented bilateral papilledema.Genetic testing revealed that the symptoms were caused by a novel gene mutation site(c.913G>A,p.D305N)in conservative domain exon-3 of NLRP3 which is gain-function gene of CINCA.The patient had the characteristic facial features,frontal fossa and saddle nose,manifested the generalized urticaria-like skin rash at two weeks after birth,periodic fever 6 months after birth,sensorineural deafness at 7 years old,and bilateral papilledema,aseptic meningitis and knee arthropathy at 9 years old.White cell counts,C-reactive protein increased and intracranial pressure raised to 300 mmH2O.The meningeal thickening enhanced by gadolinium in magnetic resonance imaging(MRI).Based on clinical features and genetic test,the girl was diagnosed bilateral papilledema secondary to CINCA and administered prednisone and lowered intracranial pressure medicine to resolve symptoms.With 3-year follow-up,patient had no inflammatory flare-up with visual acuity improvement.The finding of novel genetic mutation site(p.D305N)in NLRP3 gene expanded genotype spectrum associated with CINCA.This case also expanded the cause spectrum of papilledema and it highlighted systemic disease history for patients with bilateral papilledema.
文摘The triple A or AIIgrove＇s syndrome is an autosomal recessive disorder characterized by the triad of achalasia cardia, alacrima and ACTH resistant adrenocortical insufficiency. Mutations of the Achalasia-AddisonianismAlacrima-Syndrome （AAAS） gene on chromosome 12q13 are associated with this syndrome. We report an Indian family where two siblings were homozygous for a known mutation of the AAAS gene and presented with the classical triad of symptoms. The mother and the brother were heterozygous and asymptomatic. The affected siblings had iron deficiency anemia and the younger sister had pes cavus and palmoplantar keratosis. Neurological symptoms were absent in both affected children. Recognition of this syndrome can lead to early treatment of adrenal insufficency and genetic counselling.
文摘Meanwhile the outbreak of the Covid-19 since December, 2019 in China, it has killed more than a hundred thousand of people of all ages and sex across the globe in a short span of time. On the bases of this study the nearest family member of the virus and its receptor binding domain of S protein including its model structure and function of its active sites were naked through Multiple Sequence Alignment, modelling and molecular docking software accordingly its repository genome databases. The virus was genetically associated and molecular evolutionary related with (<em>RaTG</em>13) and it scores 96.12% homology with 99% query coverage followed by <em>bat-SL-CoVZC</em>45 and<em> bat-SL-CoVZXC</em>21 notch 89.12% and 88.65% respectively. However, SARS and MERS corona type virus those outbreak earlier respectively less likely family members of 2019-nCoV. Though the virus has a close genetic association with those previous SARS coronaviruses, and certainly the spike protein used as a binding receptor to fight against human receptor protein of ACE 2, but on the basis of FRODOC and HDOCK server analysis multi favorable active sites of S protein was discovered such GLN493 shown as a finest key in both model and possessed a unique traits on it resulting unexpected rate of transmission and number of people died while compared to the previous one. TYR500, ASN501, GLN498 and others residues preferably contemplate site also. In particular, the diversity of the virus in the world may be due to the genome structure of the virus and S gene changed over the time, across the world against to host of human genetic diversity, which may be more robust, and may be a new and unique feature. This is because it is characterized close to contact with distance divergence between wild type novel coronavirus which was risen from China against to the genomes from Lebanon, India, Italy, and USA and so on. Thus, the World Health Organization and its researchers should focus on immunologic research and effective drug and vaccine development that will help to address the epidemiology of the virus, which can provide a long-term solution.
基金supported by Beijing Municipal Administration of Hospitals’ Youth Program (QML20151003)Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (ZYLX201701)Inner Mongolia Science & Technology Plan (kjt13sf04)
文摘Gastric cancer is one of the leading causes of cancer-related deaths worldwide. Among which, about 1%–3% of gastric cancer patients were characterized by inherited gastric cancer predisposition syndromes, knowing as hereditary diffuse gastric cancer（HDGC）. Studies reported that CDH1 germline mutations are the main cause of HDGC. With the help of rapid development of genetic testing technologies and data analysis tools, more and more researchers focus on seeking candidate susceptibility genes for hereditary cancer syndromes. In addition, National Comprehensive Cancer Network（NCCN） guidelines recommend that the patients of HDGC carrying CDH1 mutations should undergo prophylactic gastrectomy or routine endoscopic surveillances. Therefore, genetic counseling plays a key role in helping individuals with pathogenic mutations make appropriate risk management plans. Moreover, experienced and professional genetic counselors as well as a systematic multidisciplinary team（MDT） are also required to facilitate the development of genetic counseling and benefit pathogenic mutation carriers who are in need of regular and standardized risk management solutions. In this review, we provided an overview about the germline mutations of several genes identified in HDGC, suggesting that these genes may potentially act as susceptibility genes for this malignant cancer syndrome. Furthermore, we introduced information for prevention, diagnosis and risk management of HDGC. Investigations on key factors that may have effect on risk management decision-making and genetic data collection of more cancer syndrome family pedigrees are required for the development of HDGC therapeutic strategies.
基金This work was supported by the National Natural Science Foundation of China[Grant No.32000832]the Shandong Province Natural Science Foundation[Grant No.ZR2020QC096].
文摘Presenilin(Psn)protein is associated with organismal aging.Mutations in the Psn gene may lead to Alzheimer’s disease(AD),dilated cardiomyopathy(DCM),and many age-dependent degenerative diseases.These diseases seriously affect the quality of life and longevity of the population and place a huge burden on health care and economic systems around the world.Humans have two types of Psn,presenilin-1(PSEN1)and presenilin-2(PSEN2).Mutations in the genes encoding PSEN1,PSEN2,and amyloid precursor protein(APP)have been identified as the major genetic causes of AD.Psn is a complex gene strongly influenced by genetic and environmental factors.The effects of exercise,training,and a high-fat diet on the Psn gene expressed in the heart and its related pathways are not fully understood.Fortunately,relevant aspects of the mutational effects on Psn can be studied experimentally in easily handled animal models,including Drosophila,mice,and other animals,all of which share orthologous genes of Psn with humans.Many previous studies have linked aging,exercise training,and a high-fat diet to the Psn gene.This review discusses the interrelationship between aging,exercise training,and a high-fat diet on the Psn gene and its associated disease,AD.The aim is to understand the adverse effects of Psn gene mutations on the body and the diseases caused by AD,find ways to alleviate the adverse effects and provide new directions for the improvement of treatment strategies for diseases caused by Psn gene mutations.
