Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in viv...Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause CMT2.Mutations located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)model.In addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive control.Of these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut allele.We found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in Drosophila.Flies heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal morphology.These Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.展开更多
BACKGROUND Thrombophilia contributes to a significant increased risk of venous thromboembolism and can be either inherited or acquired.Hereditary thrombophilia may arise from various gene mutations,some of which have ...BACKGROUND Thrombophilia contributes to a significant increased risk of venous thromboembolism and can be either inherited or acquired.Hereditary thrombophilia may arise from various gene mutations,some of which have not even been adequately reported or poorly understood.Previous studies reported a rare and novel missense mutation in the prothrombin gene(p.Arg596Gln),known as prothrombin Belgrade.The mechanisms and therapeutic strategies associated with prothrombin Belgrade mutation have not been fully elucidated.CASE SUMMARY We present the case of a 26-year-old woman with recurrent systemic thrombosis induced by prothrombin Belgrade mutation.The patient suffered from cerebral venous sinus thrombosis that rapidly progressed to systemic thrombosis,alongside a family history of cerebral thrombosis,and no traditional risk factors or abnormal coagulation function.Whole-genome sequencing detected a novel and rare heterozygous prothrombin missense mutation,c.1787G>T(p.Arg596Gln),which was responsible for the major etiology of the systemic thrombosis.CONCLUSION This case strengthens our understanding about hereditary basis of thrombophilia and provokes considerations for therapeutic options on prothrombin Belgrade mutation.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
BACKGROUND Through deeper understanding of targetable driver mutations in non-small-cell lung cancer(NSCLC)over the past years,some patients with driver mutations have benefited from the targeted molecular therapies.A...BACKGROUND Through deeper understanding of targetable driver mutations in non-small-cell lung cancer(NSCLC)over the past years,some patients with driver mutations have benefited from the targeted molecular therapies.Although the anaplastic lymphoma kinase and BRAF mutations are not frequent subtypes in NSCLC,the availability of several targeted-drugs has been confirmed through a series of clinical trials.But little is clear about the proper strategy in rare BRAF G469A mutation,not to mention co-exhibition of anaplastic lymphoma kinase and BRAF G469A mutations,which is extremely rare in NSCLC.CASE SUMMARY We present a patient to stage IVA lung adenocarcinoma with coexisting echinoderm microtubule associated protein like-4 rearrangement and BRAF G469A mutation.She received several targeted drugs with unintended resistance and suffered from unbearable adverse events.CONCLUSION Due to the rarity of co-mutations,the case not only enriches the limited literature on NSCLC harbouring BRAF G469A and echinoderm microtubule associated protein like-4 mutations,but also suggests the efficacy and safety of specific multiple-drug therapy in such patients.展开更多
Single-stranded DNA-binding proteins(SSBs)play essential roles in the replication,recombination and repair processes of organellar DNA molecules.In Arabidopsis thaliana,SSBs are encoded by a small family of two genes(...Single-stranded DNA-binding proteins(SSBs)play essential roles in the replication,recombination and repair processes of organellar DNA molecules.In Arabidopsis thaliana,SSBs are encoded by a small family of two genes(SSB1 and SSB2).However,the functional divergence of these two SSB copies in plants remains largely unknown,and detailed studies regarding their roles in the replication and recombination of organellar genomes are still incomplete.In this study,phylogenetic,gene structure and protein motif analyses all suggested that SSB1 and SSB2 probably diverged during the early evolution of seed plants.Based on accurate long-read sequencing results,ssb1 and ssb2 mutants had decreased copy numbers for both mitochondrial DNA(mtDNA)and plastid DNA(ptDNA),accompanied by a slight increase in structural rearrangements mediated by intermediate-sized repeats in mt genome and small-scale variants in both genomes.Our findings provide an important foundation for further investigating the effects of DNA dosage in the regulation of mutation frequencies in plant organellar genomes.展开更多
The use of RNA interference(RNAi)technology to control pests is explored by researchers globally.Even though RNA is a new class of pest control compound unlike conventional chemical pesticides,the evolution of pest re...The use of RNA interference(RNAi)technology to control pests is explored by researchers globally.Even though RNA is a new class of pest control compound unlike conventional chemical pesticides,the evolution of pest resistance needs to be considered.Here,we first investigate RNAi-based biopesticide resistance of Fusarium asiaticum,which is responsible for devastating diseases of plants,for example,Fusarium head blight.Five resistant strains were isolated from 500 strains that treated with UV-mutagenesis.The mutation common to all of the five resistant mutants occurred in the gene encoding Dicer2(point mutations at codon 1005 and 1007),which were under strong purifying selection pressure.To confirm whether the mutations in Dicer2 confer resistance to RNAi,we exchanged the Dicer2 locus between the sensitive strain and the resistant strain by homologous double exchange.The transformed mutants,Dicer2^(R1005D)and Dicer2^(E1007H),exhibited resistance to dsRNA in vitro.Further study showed that mutations of R1005D and E1007H affected the intramolecular interactions of Dicer2,resulting in the dysfunction of RNase III domain of Dicer2.The amount of sRNAs produced by Dicer2^(R1005D)and Dicer2^(E1007H)was extremely reduced along with variation of sRNA length.Together,these findings revealed a new potential mechanism of RNAi resistance and provided insight into RNAi-related biopesticide deployment for fungal control.展开更多
Starch biosynthesis is a complex process that relies on the coordinated action of multiple enzymes.Resistant starch is not digested in the small intestine,thus preventing a rapid rise in the glycemic index.Starch synt...Starch biosynthesis is a complex process that relies on the coordinated action of multiple enzymes.Resistant starch is not digested in the small intestine,thus preventing a rapid rise in the glycemic index.Starch synthase 2a(SS2a)is a key enzyme in amylopectin biosynthesis that has significant effects on starch structure and properties.In this study,we identified an ss2a null mutant(M3-1413)with a single base mutation from an ethyl methane sulfonate(EMS)-mutagenized population of barley.The mutation was located at the 3'end of the first intron of the RNA splicing receptor(AG)site,and resulted in abnormal RNA splicing and two abnormal transcripts of ss2a,which caused the inactivation of the SS2a gene.The starch structure and properties were significantly altered in the mutant,with M3-1413 containing lower total starch and higher amylose and resistant starch levels.This study sheds light on the effect of barley ss2a null mutations on starch properties and will help to guide new applications of barley starch in the development of nutritious food products.展开更多
BACKGROUND Pancreatic cancer(PC)is a highly malignant tumor that is resistant to chemotherapy,radiotherapy and immunotherapy.Combination chemotherapy regimens are the standard first-line regimens for metastatic diseas...BACKGROUND Pancreatic cancer(PC)is a highly malignant tumor that is resistant to chemotherapy,radiotherapy and immunotherapy.Combination chemotherapy regimens are the standard first-line regimens for metastatic disease,with a median survival<12 months.Although recurrent genomic alterations such as the BRAF V600E mutation have been reported in PC,evidence supporting the clinical effectiveness of molecularly guided targeted therapies is limited.CASE SUMMARY We report a case of a 33-year-old male who was referred to our department with weight loss of 5 kg in 2 months,anorexia and abdominal pain.Imaging showed extensive lesions involving the pancreas,liver,bones,muscles and lymph nodes accompanied by elevated carbohydrate antigen 19-9(CA19-9)and carcinoembryonic antigen(CEA).Biopsy yielded a diagnosis of PC.Treatment with gemcitabine and nab-paclitaxel was initiated,but the disease progressed in<2 months even though the patient’s general condition improved.Molecular testing revealed the presence of BRAF mutation.Dabrafenib/trametinib combination therapy was introduced,and the patient was treated for 2 months with a decrease in CA19-9 and CEA levels,but he died after 2 months of treatment.CONCLUSION BRAF alterations are infrequent in PC.This case highlights the significance of molecular profiling in patients with PC,especially in patients with a high tumor burden.展开更多
The honey badger algorithm(HBA),as a new swarm intelligence(SI)optimization algorithm,has shown certain effectiveness in its applications.Aiming at the problems of unsatisfactory initial population distribution of HBA...The honey badger algorithm(HBA),as a new swarm intelligence(SI)optimization algorithm,has shown certain effectiveness in its applications.Aiming at the problems of unsatisfactory initial population distribution of HBA,poor ability to avoid local optimum,and slow convergence speed,this paper proposes a multi-strategy improved HBA based on periodical mutation and t-distribution perturbation,called MHBA.Firstly,a good point set population initialization is introduced to get a uniform initial population.Secondly,periodic mutation and t-distribution perturbation are successively used to improve the algorithm’s ability to avoid local optimum.Finally,the density factor is improved for balancing exploration and exploitation.By comparing MHBA with HBA and 7 other SIs on 6 benchmark functions,it is evident that the performance of MHBA is far superior to HBA.In addition,by applying MHBA to robot path planning,MHBA can identify the shortest path more quickly and consistently compared with competitors.展开更多
BACKGROUND The incidence of colon cancer has been progressively increasing over time,whereas penile metastasis of colon cancer has remained exceedingly uncommon.Since the prognosis for colon cancer with BRAF_(V600E)mu...BACKGROUND The incidence of colon cancer has been progressively increasing over time,whereas penile metastasis of colon cancer has remained exceedingly uncommon.Since the prognosis for colon cancer with BRAF_(V600E)mutation is relatively unfavorable,further exploration and investigation are still required to develop treatment strategies for such rare cases.CASE SUMMARY About one year after surgery and chemotherapy,a 50-year-old patient with sigmoid colon cancer developed a mass at the base of the patient's penis,accompanied by severe tenderness and pain during urination.With disease progression,multiple metastatic nodules also emerged in other regions of the penis,including the coronal sulcus.The nodules located in the coronal sulcus were excised for histopathological examination.The histopathological findings revealed that the nodules were metastases originating from the sigmoid colon cancer,with a BRAF V600E mutation detected.This prompted a modification of the therapy regimen of cetuximab,dabrafenib and trametinib,which effectively held back the progression of penile metastasis in the patient.CONCLUSION Combining the BRAF/MEK-targeted therapy with cetuximab demonstrates a favorable therapeutic response in BRAF_(V600E)-mutated colon cancer with penile metastasis.展开更多
As the study of vascular anomalies progresses,it is imperative for plastic surgeons to individualize their in-depth research and practice to develop more effective and personalized treatment plans.Recent advancements ...As the study of vascular anomalies progresses,it is imperative for plastic surgeons to individualize their in-depth research and practice to develop more effective and personalized treatment plans.Recent advancements in genome sequencing technology have highlighted the importance of vascular endothelial growth factor(VEGF)and its receptor(VEGFR)in the formation and alteration of vascularity.However,definitive reports regarding mutations associated with this locus and treatment experiences remain scarce.Herein,we report a clinical case of multiple venous malformations with mutations in VEGFR3(FLT4).We implemented a comprehensive approach,including local lesion excision of the left foot and trunk,oral propranolol administration,and local physiotherapy.After two years of follow-up,the patient’s left foot venous malformation did not recur,and he expressed satisfaction with the outcomes of the combined therapy.This case offers valuable insights into the clinical management of this mutant type and similar presentations of multiple venous malformations.展开更多
The mutation rate is a pivotal biological characteristic,intricately governed by natural selection and historically garnering considerable attention.Recent advances in high-throughput sequencing and analytical methodo...The mutation rate is a pivotal biological characteristic,intricately governed by natural selection and historically garnering considerable attention.Recent advances in high-throughput sequencing and analytical methodologies have profoundly transformed our understanding in this domain,ushering in an unprecedented era of mutation rate research.This paper aims to provide a comprehensive overview of the key concepts and methodologies frequently employed in the study of mutation rates.It examines various types of mutations,explores the evolutionary dynamics and associated theories,and synthesizes both classical and contemporary hypotheses.Furthermore,this review comprehensively explores recent advances in understanding germline and somatic mutations in animals and offers an overview of experimental methodologies,mutational patterns,molecular mechanisms,and driving forces influencing variations in mutation rates across species and tissues.Finally,it proposes several potential research directions and pressing questions for future investigations.展开更多
●AIM:To investigate the molecular diagnosis of a threegeneration Chinese family affected with aniridia,and further to identify clinically a PAX6 missense mutation in members with atypical aniridia.●METHODS:Eleven fa...●AIM:To investigate the molecular diagnosis of a threegeneration Chinese family affected with aniridia,and further to identify clinically a PAX6 missense mutation in members with atypical aniridia.●METHODS:Eleven family members with and without atypical aniridia were recruited.All family members underwent comprehensive ophthalmic examinations.A combination of whole exome sequencing(WES)and direct Sanger sequencing were performed to uncover the causative mutation.●RESULTS:Among the 11 family members,8 were clinically diagnosed with congenital aniridia(atypical aniridia phenotype).A rare heterozygous mutation c.622C>T(p.Arg208Trp)in exon 8 of PAX6 was identified in all affected family members but not in the unaffected members or in healthy control subjects.●CONCLUSION:A rare missense mutation in the PAX6 gene is found in members of a three-generation Chinese family with congenital atypical aniridia.This result contributes to an increase in the phenotypic spectrum caused by PAX6 missense heterozygous variants and provides useful information for the clinical diagnosis of atypical aniridia,which may also contribute to genetic counselling and family planning.展开更多
Genetic algorithms(GAs)are very good metaheuristic algorithms that are suitable for solving NP-hard combinatorial optimization problems.AsimpleGAbeginswith a set of solutions represented by a population of chromosomes...Genetic algorithms(GAs)are very good metaheuristic algorithms that are suitable for solving NP-hard combinatorial optimization problems.AsimpleGAbeginswith a set of solutions represented by a population of chromosomes and then uses the idea of survival of the fittest in the selection process to select some fitter chromosomes.It uses a crossover operator to create better offspring chromosomes and thus,converges the population.Also,it uses a mutation operator to explore the unexplored areas by the crossover operator,and thus,diversifies the GA search space.A combination of crossover and mutation operators makes the GA search strong enough to reach the optimal solution.However,appropriate selection and combination of crossover operator and mutation operator can lead to a very good GA for solving an optimization problem.In this present paper,we aim to study the benchmark traveling salesman problem(TSP).We developed several genetic algorithms using seven crossover operators and six mutation operators for the TSP and then compared them to some benchmark TSPLIB instances.The experimental studies show the effectiveness of the combination of a comprehensive sequential constructive crossover operator and insertion mutation operator for the problem.The GA using the comprehensive sequential constructive crossover with insertion mutation could find average solutions whose average percentage of excesses from the best-known solutions are between 0.22 and 14.94 for our experimented problem instances.展开更多
To the editor:In a recent article published in Pediatric Investigation,Zhang et al.reported a case series of phacomatosis pigmentovascularis(PPV).1 Among such cases,one was described as featuring an extensive laterali...To the editor:In a recent article published in Pediatric Investigation,Zhang et al.reported a case series of phacomatosis pigmentovascularis(PPV).1 Among such cases,one was described as featuring an extensive lateralized telangiectatic nevus,a large hypermelanotic patch and a Klippel-Trenaunay phenotype;and another an extensive lateralised telangiectatic nevus,a nevus anemicus,an extensive nevus cesius,a large hypermelanotic patch and a Sturge-Weber-Klippel-Trenaunay phenotype.1 These cases were diagnosed as unclassifiable PPV and phacomatosis cesioflammea;instead,their clinical features are compatible with phacomatosis melanorosea(PMR)and phacomatosis melanocesioflammea(PMCF),respectively.展开更多
The severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)belongs to the genus Beta coronavirus and the family of Coronaviridae.It is a positive-sense,non-segmented single-strand RNA virus.Four common types of hu...The severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)belongs to the genus Beta coronavirus and the family of Coronaviridae.It is a positive-sense,non-segmented single-strand RNA virus.Four common types of human coronaviruses circulate globally,particularly in the fall and winter seasons.They are responsible for 10%-30% of all mild upper respiratory tract infections in adults.These are 229E,NL63 of the Alfacoronaviridae family,OC43,and HKU1 of the Betacoronaviridae family.However,there are three highly pathogenic human coronaviruses:SARS-CoV-2,Middle East respiratory syndrome coronavirus,and the latest pandemic caused by the SARS-CoV-2 infection.All viruses,including SARS-CoV-2,have the inherent tendency to evolve.SARS-CoV-2 is still evolving in humans.Additionally,due to the development of herd immunity,prior infection,use of medication,vaccination,and antibodies,the viruses are facing immune pressure.During the replication process and due to immune pressure,the virus may undergo mutations.Several SARS-CoV-2 variants,including the variants of concern(VOCs),such as B.1.1.7(Alpha),B.1.351(Beta),B.1.617/B.1.617.2(Delta),P.1(Gamma),and B.1.1.529(Omicron)have been reported from various parts of the world.These VOCs contain several important mutations;some of them are on the spike proteins.These mutations may lead to enhanced infectivity,transmissibility,and decreased neutralization efficacy by monoclonal antibodies,convalescent sera,or vaccines.Mutations may also lead to a failure of detection by molecular diagnostic tests,leading to a delayed diagnosis,increased community spread,and delayed treatment.We searched PubMed,EMBASE,Covariant,the Stanford variant Database,and the CINAHL from December 2019 to February 2023 using the following search terms:VOC,SARS-CoV-2,Omicron,mutations in SARS-CoV-2,etc.This review discusses the various mutations and their impact on infectivity,transmissibility,and neutralization efficacy.展开更多
Identified as the pathogenic genes of Alzheimer's disease(AD),APP,PSEN1,and PSEN2 mainly lead to early-onset AD,whose course is more aggressive,and atypical symptoms are more common than sporadic AD.Here,a novel m...Identified as the pathogenic genes of Alzheimer's disease(AD),APP,PSEN1,and PSEN2 mainly lead to early-onset AD,whose course is more aggressive,and atypical symptoms are more common than sporadic AD.Here,a novel missense mutation,APP E674Q(also named“Shanghai APP”),was detected in a Chinese index patient with typical late-onset AD(LOAD)who developed memory decline in his mid-70s.The results from neuroimaging were consistent with AD,where widespread amyloidβdeposition was demonstrated in 18 F-florbetapir Positron Emission Tomography(PET).APP E674Q is close to theβ-secretase cleavage site and the well-studied Swedish APP mutation(KM670/671NL),which was predicted to be pathogenic in silico.Molecular dynamics simulation indicated that the E674Q mutation resulted in a rearrangement of the interaction mode between APP and BACE1 and that the E674Q mutation was more prone to cleavage by BACE1.The in vitro results suggested that the E674Q mutation was pathogenic by facilitating the BACE1-mediated processing of APP and the production of Aβ.Furthermore,we applied an adeno-associated virus(AAV)-mediated transfer of the human E674Q mutant APP gene to the hippocampi of two-month-old C57Bl/6 J mice.AAV-E674Q-injected mice exhibited impaired learning behavior and increased pathological burden in the brain,implying that the E674Q mutation had a pathogenicity that bore a comparison with the classical Swedish mutation.Collectively,we report a strong amyloidogenic effect of the E674Q substitution in AD.To our knowledge,E674Q is the only pathogenic mutation within the amyloid processing sequence causing LOAD.展开更多
Agrobacterium-mediated plant transformation is widely used in plant genetic engineering.However,its efficiency is limited by plant immunity against Agrobacterium.Chili pepper(Capsicum annuum L.)is an important vegetab...Agrobacterium-mediated plant transformation is widely used in plant genetic engineering.However,its efficiency is limited by plant immunity against Agrobacterium.Chili pepper(Capsicum annuum L.)is an important vegetable that is recalcitrant to Agrobacterium-mediated transformation.In this work,Agrobacterium was found to induce a strong immune response in pepper,which might be the reason for T-DNA being difficult to express in pepper.An Agrobacterium mutant screen was conducted and a point mutation in the hisI gene was identified due to a weak immune response and enhanced transient expression mediated by this Agrobacterium mutant in pepper leaves.Further genetic analysis revealed that histidine biosynthesis deficiency caused by mutations in many genes of this pathway led to reduced pepper cell death,presumably due to reduced bacterial growth.However,mutation analysis of threonine and tryptophan biosynthesis genes showed that the biosynthesis of different amino acids may play different roles in Agrobacterium growth and stimulating the pepper immune response.The possible application of Agrobacterium amino acid biosynthesis mutations in plant biology was discussed.展开更多
BACKGROUND The SETD1B gene is instrumental in human intelligence and nerve development.Mutations in the SETD1B gene have been linked in recent studies to neurodevelopmental disorders,seizures,and language delay.CASE S...BACKGROUND The SETD1B gene is instrumental in human intelligence and nerve development.Mutations in the SETD1B gene have been linked in recent studies to neurodevelopmental disorders,seizures,and language delay.CASE SUMMARY This study aimed to analyze the clinical manifestations and treatment of three patients suffering from mental retardation,epilepsy,and language delay resulting from a new mutation in the SETD1B gene.Three individuals with these symptoms were selected,and their clinical symptoms,gene test results,and treatment were analyzed.This article discusses the impact of the SETD1B gene mutation on patients and outlines the treatment approach.Among the three patients(two females and one male,aged 8,4,and 1,respectively),all exhibited psychomotor retardation,attention deficit,and hyperactivity disorder,and two had epilepsy.Antiepileptic treatment with sodium tripolyvalproate halted the seizures in the affected child,although mental development remained somewhat delayed.Whole exome sequencing revealed new mutations in the SETD1B gene for all patients,specifically with c.5473C>T(p.Arg1825trp),c.4120C>T(p.Gln1374*,593),c.14_15insC(p.His5Hisfs*33).CONCLUSION Possessing the SETD1B gene mutation may cause mental retardation accompanied by seizures and language delay.Although the exact mechanism is not fully understood,interventions such as drug therapy,rehabilitation training,and family support can assist patients in managing their symptoms and enhancing their quality of life.Furthermore,genetic testing supplies healthcare providers with more precise diagnostic and therapeutic guidance,informs families about genetic disease risks,and contributes to understanding disease pathogenesis and drug research and development.展开更多
BACKGROUND Multiple endocrine neoplasia type 2(MEN2)is a rare,autosomal dominant endocrine disease.Currently,the RET proto-oncogene is the only gene implicated in MEN2A pathogenesis.Once an RET carrier is detected,fam...BACKGROUND Multiple endocrine neoplasia type 2(MEN2)is a rare,autosomal dominant endocrine disease.Currently,the RET proto-oncogene is the only gene implicated in MEN2A pathogenesis.Once an RET carrier is detected,family members should be screened to enable early detection of medullary thyroid carcinoma,pheochromocytoma,and hyperparatitity.Among these,medullary thyroid carcinoma is the main factor responsible for patient mortality.Accordingly,delineating strategies to inform clinical follow-up and treatment plans based on genes is paramount for clinical practitioners.CASE SUMMARY Herein,we present RET proto-oncogene mutations,clinical characteristics,and treatment strategies in a family with MEN2A.A family study was conducted on patients diagnosed with MEN2A.DNA was extracted from the peripheral blood of family members,and first-generation exon sequencing of the RET protooncogene was conducted.The C634Y mutation was identified in three family members spanning three generations.Two patients were sequentially diagnosed with pheochromocytomas and bilateral medullary thyroid carcinomas.A 9-yearold child harboring the gene mutation was diagnosed with medullary thyroid carcinoma.Surgical resection of the tumors was performed.All family members were advised to undergo complete genetic testing related to the C634Y mutation,and the corresponding treatments administered based on test results and associated clinical guidelines.CONCLUSION Advancements in MEN2A research are important for familial management,assessment of medullary thyroid cancer invasive risk,and deciding surgical timing.展开更多
基金supported by the Natural Science Foundation of Fujian Province,No.2020J02027the National Natural Science Foundation of China,No.31970461the Foundation of NHC Key Laboratory of Technical Evaluation of Fertility Regulation for Non-human Primate,Fujian Maternity and Child Health Hospital,No.2022-NHP-05(all to WC).
文摘Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause CMT2.Mutations located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)model.In addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive control.Of these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut allele.We found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in Drosophila.Flies heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal morphology.These Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.
文摘BACKGROUND Thrombophilia contributes to a significant increased risk of venous thromboembolism and can be either inherited or acquired.Hereditary thrombophilia may arise from various gene mutations,some of which have not even been adequately reported or poorly understood.Previous studies reported a rare and novel missense mutation in the prothrombin gene(p.Arg596Gln),known as prothrombin Belgrade.The mechanisms and therapeutic strategies associated with prothrombin Belgrade mutation have not been fully elucidated.CASE SUMMARY We present the case of a 26-year-old woman with recurrent systemic thrombosis induced by prothrombin Belgrade mutation.The patient suffered from cerebral venous sinus thrombosis that rapidly progressed to systemic thrombosis,alongside a family history of cerebral thrombosis,and no traditional risk factors or abnormal coagulation function.Whole-genome sequencing detected a novel and rare heterozygous prothrombin missense mutation,c.1787G>T(p.Arg596Gln),which was responsible for the major etiology of the systemic thrombosis.CONCLUSION This case strengthens our understanding about hereditary basis of thrombophilia and provokes considerations for therapeutic options on prothrombin Belgrade mutation.
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.
基金Supported by the Medical Education Collaborative Innovation Fund of Jiangsu University,No.JDY2022015。
文摘BACKGROUND Through deeper understanding of targetable driver mutations in non-small-cell lung cancer(NSCLC)over the past years,some patients with driver mutations have benefited from the targeted molecular therapies.Although the anaplastic lymphoma kinase and BRAF mutations are not frequent subtypes in NSCLC,the availability of several targeted-drugs has been confirmed through a series of clinical trials.But little is clear about the proper strategy in rare BRAF G469A mutation,not to mention co-exhibition of anaplastic lymphoma kinase and BRAF G469A mutations,which is extremely rare in NSCLC.CASE SUMMARY We present a patient to stage IVA lung adenocarcinoma with coexisting echinoderm microtubule associated protein like-4 rearrangement and BRAF G469A mutation.She received several targeted drugs with unintended resistance and suffered from unbearable adverse events.CONCLUSION Due to the rarity of co-mutations,the case not only enriches the limited literature on NSCLC harbouring BRAF G469A and echinoderm microtubule associated protein like-4 mutations,but also suggests the efficacy and safety of specific multiple-drug therapy in such patients.
基金supported by grants from the National Natural Science Foundation of China(32170238,32400191)Guangdong Basic and Applied Basic Research Foundation(2023A1515111029)+2 种基金the Science,Technology and Innovation Commission of Shenzhen Municipality(RCYX20200714114538196)the Chinese Academy of Agricultural Sciences Elite Youth Program(grant 110243160001007)the Guangdong Pearl River Talent Program(2021QN02N792)。
文摘Single-stranded DNA-binding proteins(SSBs)play essential roles in the replication,recombination and repair processes of organellar DNA molecules.In Arabidopsis thaliana,SSBs are encoded by a small family of two genes(SSB1 and SSB2).However,the functional divergence of these two SSB copies in plants remains largely unknown,and detailed studies regarding their roles in the replication and recombination of organellar genomes are still incomplete.In this study,phylogenetic,gene structure and protein motif analyses all suggested that SSB1 and SSB2 probably diverged during the early evolution of seed plants.Based on accurate long-read sequencing results,ssb1 and ssb2 mutants had decreased copy numbers for both mitochondrial DNA(mtDNA)and plastid DNA(ptDNA),accompanied by a slight increase in structural rearrangements mediated by intermediate-sized repeats in mt genome and small-scale variants in both genomes.Our findings provide an important foundation for further investigating the effects of DNA dosage in the regulation of mutation frequencies in plant organellar genomes.
基金funded by the National Natural Science Foundation of China(32372585)the Natural Science Foundation of Jiangsu Province,China(BK20231471)the National Training Program of Innovation and Entrepreneurship for Undergraduates,China(202210307013Z)。
文摘The use of RNA interference(RNAi)technology to control pests is explored by researchers globally.Even though RNA is a new class of pest control compound unlike conventional chemical pesticides,the evolution of pest resistance needs to be considered.Here,we first investigate RNAi-based biopesticide resistance of Fusarium asiaticum,which is responsible for devastating diseases of plants,for example,Fusarium head blight.Five resistant strains were isolated from 500 strains that treated with UV-mutagenesis.The mutation common to all of the five resistant mutants occurred in the gene encoding Dicer2(point mutations at codon 1005 and 1007),which were under strong purifying selection pressure.To confirm whether the mutations in Dicer2 confer resistance to RNAi,we exchanged the Dicer2 locus between the sensitive strain and the resistant strain by homologous double exchange.The transformed mutants,Dicer2^(R1005D)and Dicer2^(E1007H),exhibited resistance to dsRNA in vitro.Further study showed that mutations of R1005D and E1007H affected the intramolecular interactions of Dicer2,resulting in the dysfunction of RNase III domain of Dicer2.The amount of sRNAs produced by Dicer2^(R1005D)and Dicer2^(E1007H)was extremely reduced along with variation of sRNA length.Together,these findings revealed a new potential mechanism of RNAi resistance and provided insight into RNAi-related biopesticide deployment for fungal control.
基金supported by the Major Program of National Agricultural Science and Technology of China(NK20220607)the Sichuan Science and Technology Program,China(2023YFH0041)。
文摘Starch biosynthesis is a complex process that relies on the coordinated action of multiple enzymes.Resistant starch is not digested in the small intestine,thus preventing a rapid rise in the glycemic index.Starch synthase 2a(SS2a)is a key enzyme in amylopectin biosynthesis that has significant effects on starch structure and properties.In this study,we identified an ss2a null mutant(M3-1413)with a single base mutation from an ethyl methane sulfonate(EMS)-mutagenized population of barley.The mutation was located at the 3'end of the first intron of the RNA splicing receptor(AG)site,and resulted in abnormal RNA splicing and two abnormal transcripts of ss2a,which caused the inactivation of the SS2a gene.The starch structure and properties were significantly altered in the mutant,with M3-1413 containing lower total starch and higher amylose and resistant starch levels.This study sheds light on the effect of barley ss2a null mutations on starch properties and will help to guide new applications of barley starch in the development of nutritious food products.
基金Supported by Clinical Research Center for Precision Medicine of Abdominal Tumor of Fujian Province.
文摘BACKGROUND Pancreatic cancer(PC)is a highly malignant tumor that is resistant to chemotherapy,radiotherapy and immunotherapy.Combination chemotherapy regimens are the standard first-line regimens for metastatic disease,with a median survival<12 months.Although recurrent genomic alterations such as the BRAF V600E mutation have been reported in PC,evidence supporting the clinical effectiveness of molecularly guided targeted therapies is limited.CASE SUMMARY We report a case of a 33-year-old male who was referred to our department with weight loss of 5 kg in 2 months,anorexia and abdominal pain.Imaging showed extensive lesions involving the pancreas,liver,bones,muscles and lymph nodes accompanied by elevated carbohydrate antigen 19-9(CA19-9)and carcinoembryonic antigen(CEA).Biopsy yielded a diagnosis of PC.Treatment with gemcitabine and nab-paclitaxel was initiated,but the disease progressed in<2 months even though the patient’s general condition improved.Molecular testing revealed the presence of BRAF mutation.Dabrafenib/trametinib combination therapy was introduced,and the patient was treated for 2 months with a decrease in CA19-9 and CEA levels,but he died after 2 months of treatment.CONCLUSION BRAF alterations are infrequent in PC.This case highlights the significance of molecular profiling in patients with PC,especially in patients with a high tumor burden.
基金Supported by the National Key Research and Development Program of China(No.2022ZD0119001)。
文摘The honey badger algorithm(HBA),as a new swarm intelligence(SI)optimization algorithm,has shown certain effectiveness in its applications.Aiming at the problems of unsatisfactory initial population distribution of HBA,poor ability to avoid local optimum,and slow convergence speed,this paper proposes a multi-strategy improved HBA based on periodical mutation and t-distribution perturbation,called MHBA.Firstly,a good point set population initialization is introduced to get a uniform initial population.Secondly,periodic mutation and t-distribution perturbation are successively used to improve the algorithm’s ability to avoid local optimum.Finally,the density factor is improved for balancing exploration and exploitation.By comparing MHBA with HBA and 7 other SIs on 6 benchmark functions,it is evident that the performance of MHBA is far superior to HBA.In addition,by applying MHBA to robot path planning,MHBA can identify the shortest path more quickly and consistently compared with competitors.
基金National Natural Science Foundation of China,No.81871981Natural Science Foundation of Guangdong Province,No.2022A1515012348 and No.2023A1515010457.
文摘BACKGROUND The incidence of colon cancer has been progressively increasing over time,whereas penile metastasis of colon cancer has remained exceedingly uncommon.Since the prognosis for colon cancer with BRAF_(V600E)mutation is relatively unfavorable,further exploration and investigation are still required to develop treatment strategies for such rare cases.CASE SUMMARY About one year after surgery and chemotherapy,a 50-year-old patient with sigmoid colon cancer developed a mass at the base of the patient's penis,accompanied by severe tenderness and pain during urination.With disease progression,multiple metastatic nodules also emerged in other regions of the penis,including the coronal sulcus.The nodules located in the coronal sulcus were excised for histopathological examination.The histopathological findings revealed that the nodules were metastases originating from the sigmoid colon cancer,with a BRAF V600E mutation detected.This prompted a modification of the therapy regimen of cetuximab,dabrafenib and trametinib,which effectively held back the progression of penile metastasis in the patient.CONCLUSION Combining the BRAF/MEK-targeted therapy with cetuximab demonstrates a favorable therapeutic response in BRAF_(V600E)-mutated colon cancer with penile metastasis.
基金supported by the National Natural Science Foundation of China(grant no.82272891).
文摘As the study of vascular anomalies progresses,it is imperative for plastic surgeons to individualize their in-depth research and practice to develop more effective and personalized treatment plans.Recent advancements in genome sequencing technology have highlighted the importance of vascular endothelial growth factor(VEGF)and its receptor(VEGFR)in the formation and alteration of vascularity.However,definitive reports regarding mutations associated with this locus and treatment experiences remain scarce.Herein,we report a clinical case of multiple venous malformations with mutations in VEGFR3(FLT4).We implemented a comprehensive approach,including local lesion excision of the left foot and trunk,oral propranolol administration,and local physiotherapy.After two years of follow-up,the patient’s left foot venous malformation did not recur,and he expressed satisfaction with the outcomes of the combined therapy.This case offers valuable insights into the clinical management of this mutant type and similar presentations of multiple venous malformations.
文摘The mutation rate is a pivotal biological characteristic,intricately governed by natural selection and historically garnering considerable attention.Recent advances in high-throughput sequencing and analytical methodologies have profoundly transformed our understanding in this domain,ushering in an unprecedented era of mutation rate research.This paper aims to provide a comprehensive overview of the key concepts and methodologies frequently employed in the study of mutation rates.It examines various types of mutations,explores the evolutionary dynamics and associated theories,and synthesizes both classical and contemporary hypotheses.Furthermore,this review comprehensively explores recent advances in understanding germline and somatic mutations in animals and offers an overview of experimental methodologies,mutational patterns,molecular mechanisms,and driving forces influencing variations in mutation rates across species and tissues.Finally,it proposes several potential research directions and pressing questions for future investigations.
文摘●AIM:To investigate the molecular diagnosis of a threegeneration Chinese family affected with aniridia,and further to identify clinically a PAX6 missense mutation in members with atypical aniridia.●METHODS:Eleven family members with and without atypical aniridia were recruited.All family members underwent comprehensive ophthalmic examinations.A combination of whole exome sequencing(WES)and direct Sanger sequencing were performed to uncover the causative mutation.●RESULTS:Among the 11 family members,8 were clinically diagnosed with congenital aniridia(atypical aniridia phenotype).A rare heterozygous mutation c.622C>T(p.Arg208Trp)in exon 8 of PAX6 was identified in all affected family members but not in the unaffected members or in healthy control subjects.●CONCLUSION:A rare missense mutation in the PAX6 gene is found in members of a three-generation Chinese family with congenital atypical aniridia.This result contributes to an increase in the phenotypic spectrum caused by PAX6 missense heterozygous variants and provides useful information for the clinical diagnosis of atypical aniridia,which may also contribute to genetic counselling and family planning.
基金the Deanship of Scientific Research at Imam Mohammad Ibn Saud Islamic University(IMSIU)(Grant Number IMSIU-RP23030).
文摘Genetic algorithms(GAs)are very good metaheuristic algorithms that are suitable for solving NP-hard combinatorial optimization problems.AsimpleGAbeginswith a set of solutions represented by a population of chromosomes and then uses the idea of survival of the fittest in the selection process to select some fitter chromosomes.It uses a crossover operator to create better offspring chromosomes and thus,converges the population.Also,it uses a mutation operator to explore the unexplored areas by the crossover operator,and thus,diversifies the GA search space.A combination of crossover and mutation operators makes the GA search strong enough to reach the optimal solution.However,appropriate selection and combination of crossover operator and mutation operator can lead to a very good GA for solving an optimization problem.In this present paper,we aim to study the benchmark traveling salesman problem(TSP).We developed several genetic algorithms using seven crossover operators and six mutation operators for the TSP and then compared them to some benchmark TSPLIB instances.The experimental studies show the effectiveness of the combination of a comprehensive sequential constructive crossover operator and insertion mutation operator for the problem.The GA using the comprehensive sequential constructive crossover with insertion mutation could find average solutions whose average percentage of excesses from the best-known solutions are between 0.22 and 14.94 for our experimented problem instances.
文摘To the editor:In a recent article published in Pediatric Investigation,Zhang et al.reported a case series of phacomatosis pigmentovascularis(PPV).1 Among such cases,one was described as featuring an extensive lateralized telangiectatic nevus,a large hypermelanotic patch and a Klippel-Trenaunay phenotype;and another an extensive lateralised telangiectatic nevus,a nevus anemicus,an extensive nevus cesius,a large hypermelanotic patch and a Sturge-Weber-Klippel-Trenaunay phenotype.1 These cases were diagnosed as unclassifiable PPV and phacomatosis cesioflammea;instead,their clinical features are compatible with phacomatosis melanorosea(PMR)and phacomatosis melanocesioflammea(PMCF),respectively.
文摘The severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)belongs to the genus Beta coronavirus and the family of Coronaviridae.It is a positive-sense,non-segmented single-strand RNA virus.Four common types of human coronaviruses circulate globally,particularly in the fall and winter seasons.They are responsible for 10%-30% of all mild upper respiratory tract infections in adults.These are 229E,NL63 of the Alfacoronaviridae family,OC43,and HKU1 of the Betacoronaviridae family.However,there are three highly pathogenic human coronaviruses:SARS-CoV-2,Middle East respiratory syndrome coronavirus,and the latest pandemic caused by the SARS-CoV-2 infection.All viruses,including SARS-CoV-2,have the inherent tendency to evolve.SARS-CoV-2 is still evolving in humans.Additionally,due to the development of herd immunity,prior infection,use of medication,vaccination,and antibodies,the viruses are facing immune pressure.During the replication process and due to immune pressure,the virus may undergo mutations.Several SARS-CoV-2 variants,including the variants of concern(VOCs),such as B.1.1.7(Alpha),B.1.351(Beta),B.1.617/B.1.617.2(Delta),P.1(Gamma),and B.1.1.529(Omicron)have been reported from various parts of the world.These VOCs contain several important mutations;some of them are on the spike proteins.These mutations may lead to enhanced infectivity,transmissibility,and decreased neutralization efficacy by monoclonal antibodies,convalescent sera,or vaccines.Mutations may also lead to a failure of detection by molecular diagnostic tests,leading to a delayed diagnosis,increased community spread,and delayed treatment.We searched PubMed,EMBASE,Covariant,the Stanford variant Database,and the CINAHL from December 2019 to February 2023 using the following search terms:VOC,SARS-CoV-2,Omicron,mutations in SARS-CoV-2,etc.This review discusses the various mutations and their impact on infectivity,transmissibility,and neutralization efficacy.
基金supported by grants from the Ministry of Science and Technology of the People's Republic of China(No.2021ZD020180)the Natural Science Foundation of China(No.81971068,81922021,81773635,82073765).
文摘Identified as the pathogenic genes of Alzheimer's disease(AD),APP,PSEN1,and PSEN2 mainly lead to early-onset AD,whose course is more aggressive,and atypical symptoms are more common than sporadic AD.Here,a novel missense mutation,APP E674Q(also named“Shanghai APP”),was detected in a Chinese index patient with typical late-onset AD(LOAD)who developed memory decline in his mid-70s.The results from neuroimaging were consistent with AD,where widespread amyloidβdeposition was demonstrated in 18 F-florbetapir Positron Emission Tomography(PET).APP E674Q is close to theβ-secretase cleavage site and the well-studied Swedish APP mutation(KM670/671NL),which was predicted to be pathogenic in silico.Molecular dynamics simulation indicated that the E674Q mutation resulted in a rearrangement of the interaction mode between APP and BACE1 and that the E674Q mutation was more prone to cleavage by BACE1.The in vitro results suggested that the E674Q mutation was pathogenic by facilitating the BACE1-mediated processing of APP and the production of Aβ.Furthermore,we applied an adeno-associated virus(AAV)-mediated transfer of the human E674Q mutant APP gene to the hippocampi of two-month-old C57Bl/6 J mice.AAV-E674Q-injected mice exhibited impaired learning behavior and increased pathological burden in the brain,implying that the E674Q mutation had a pathogenicity that bore a comparison with the classical Swedish mutation.Collectively,we report a strong amyloidogenic effect of the E674Q substitution in AD.To our knowledge,E674Q is the only pathogenic mutation within the amyloid processing sequence causing LOAD.
基金supported by the National Key Research and Development Program of China(Grant No.2018YFD1000800)National Natural Science Foundation of China(Grant No.32172600)。
文摘Agrobacterium-mediated plant transformation is widely used in plant genetic engineering.However,its efficiency is limited by plant immunity against Agrobacterium.Chili pepper(Capsicum annuum L.)is an important vegetable that is recalcitrant to Agrobacterium-mediated transformation.In this work,Agrobacterium was found to induce a strong immune response in pepper,which might be the reason for T-DNA being difficult to express in pepper.An Agrobacterium mutant screen was conducted and a point mutation in the hisI gene was identified due to a weak immune response and enhanced transient expression mediated by this Agrobacterium mutant in pepper leaves.Further genetic analysis revealed that histidine biosynthesis deficiency caused by mutations in many genes of this pathway led to reduced pepper cell death,presumably due to reduced bacterial growth.However,mutation analysis of threonine and tryptophan biosynthesis genes showed that the biosynthesis of different amino acids may play different roles in Agrobacterium growth and stimulating the pepper immune response.The possible application of Agrobacterium amino acid biosynthesis mutations in plant biology was discussed.
基金Key Health Science and Technology Development Project of Nanjing City,Jiangsu Province,No.ZKX19038.
文摘BACKGROUND The SETD1B gene is instrumental in human intelligence and nerve development.Mutations in the SETD1B gene have been linked in recent studies to neurodevelopmental disorders,seizures,and language delay.CASE SUMMARY This study aimed to analyze the clinical manifestations and treatment of three patients suffering from mental retardation,epilepsy,and language delay resulting from a new mutation in the SETD1B gene.Three individuals with these symptoms were selected,and their clinical symptoms,gene test results,and treatment were analyzed.This article discusses the impact of the SETD1B gene mutation on patients and outlines the treatment approach.Among the three patients(two females and one male,aged 8,4,and 1,respectively),all exhibited psychomotor retardation,attention deficit,and hyperactivity disorder,and two had epilepsy.Antiepileptic treatment with sodium tripolyvalproate halted the seizures in the affected child,although mental development remained somewhat delayed.Whole exome sequencing revealed new mutations in the SETD1B gene for all patients,specifically with c.5473C>T(p.Arg1825trp),c.4120C>T(p.Gln1374*,593),c.14_15insC(p.His5Hisfs*33).CONCLUSION Possessing the SETD1B gene mutation may cause mental retardation accompanied by seizures and language delay.Although the exact mechanism is not fully understood,interventions such as drug therapy,rehabilitation training,and family support can assist patients in managing their symptoms and enhancing their quality of life.Furthermore,genetic testing supplies healthcare providers with more precise diagnostic and therapeutic guidance,informs families about genetic disease risks,and contributes to understanding disease pathogenesis and drug research and development.
基金Supported by The Finance Bureau of Dongguan City,Guangdong Province.
文摘BACKGROUND Multiple endocrine neoplasia type 2(MEN2)is a rare,autosomal dominant endocrine disease.Currently,the RET proto-oncogene is the only gene implicated in MEN2A pathogenesis.Once an RET carrier is detected,family members should be screened to enable early detection of medullary thyroid carcinoma,pheochromocytoma,and hyperparatitity.Among these,medullary thyroid carcinoma is the main factor responsible for patient mortality.Accordingly,delineating strategies to inform clinical follow-up and treatment plans based on genes is paramount for clinical practitioners.CASE SUMMARY Herein,we present RET proto-oncogene mutations,clinical characteristics,and treatment strategies in a family with MEN2A.A family study was conducted on patients diagnosed with MEN2A.DNA was extracted from the peripheral blood of family members,and first-generation exon sequencing of the RET protooncogene was conducted.The C634Y mutation was identified in three family members spanning three generations.Two patients were sequentially diagnosed with pheochromocytomas and bilateral medullary thyroid carcinomas.A 9-yearold child harboring the gene mutation was diagnosed with medullary thyroid carcinoma.Surgical resection of the tumors was performed.All family members were advised to undergo complete genetic testing related to the C634Y mutation,and the corresponding treatments administered based on test results and associated clinical guidelines.CONCLUSION Advancements in MEN2A research are important for familial management,assessment of medullary thyroid cancer invasive risk,and deciding surgical timing.
