Polyembryony has posed a significant impediment to the advancement of citrus hybrid breeding.FhRWP is widely regarded as a pivotal factor governing asexual reproduction in citrus,and prior research has demonstrated th...Polyembryony has posed a significant impediment to the advancement of citrus hybrid breeding.FhRWP is widely regarded as a pivotal factor governing asexual reproduction in citrus,and prior research has demonstrated that FhARID1,acting as an upstream regulator,modulates FhRWP expression.In this study,we performed a genome-wide characterization of the ARID-HMG-related genes using the short juvenile minicitrus Fortunella hindsii.A total of 20 ARID-HMG-related genes were identified.Protein interaction network and enrichment analysis suggested that ARID-HMG-related proteins might might be involved in chromatin remodeling complexes.Knockout of FhARID1 in F.hindsii did not induce the conversion from polyembryony to monoembryony.However,fharid1 plants in T1 generation exhibited abnormal proliferation at axillary buds,which is similar to phenotype of fhrwp plants.Expression analysis of fharid1 ovary tissues revealed the downregulation of FhRWP.The results indicated that FhARID1,as an upstream regulator of FhRWP,has an effect on the development of citrus axillary buds.Expression analysis of overexpressed leaves of FhARID1 lines showed that no significant up-regulation of FhRWP,indicating that FhARID1 is not the sole upstream regulatory factor of FhRWP.Only FhARID2 showed a correlation in expression with FhARID1 among the ARID-related genes,further supporting the notion that this gene may be involved in complex formation rather than acting alone.Yeast two-hybrid and MS/MS spectra further indicated that FhARID1 function requires casein kinase II-mediated post-transcriptional phosphorylation.This study elucidated the function of FhARID1 in citrus apomixis and axillary bud development,providing a fundamental basis for understanding the role of ARID-HMG-related genes.展开更多
Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-asso...Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.展开更多
Objective To investigate the structural changes of rat thoracic aorta and changes in expression levels of Bmal1 and cyclins in thoracic aorta endothelial cells following heat stress.Methods Twenty male SD rats were ra...Objective To investigate the structural changes of rat thoracic aorta and changes in expression levels of Bmal1 and cyclins in thoracic aorta endothelial cells following heat stress.Methods Twenty male SD rats were randomized equally into control group and heat stress group.After exposure to 32℃for 2 weeks in the latter group,the rats were examined for histopathological changes and Bmal1 expression in the thoracic aorta using HE staining and immunohistochemistry.In the cell experiments,cultured rat thoracic aortic endothelial cells(RTAECs)were incubated at 40℃for 12 h with or without prior transfection with a Bmal1-specific small interfering RNA(si-Bmal1)or a negative sequence.In both rat thoracic aorta and RTAECs,the expressions of Bmal1,the cell cycle proteins CDK1,CDK4,CDK6,and cyclin B1,and apoptosis-related proteins Bax and Bcl-2 were detected using Western blotting.TUNEL staining was used to detect cell apoptosis in rat thoracic aorta,and the changes in cell cycle distribution and apoptosis in RTAECs were analyzed with flow cytometry.Results Compared with the control rats,the rats exposed to heat stress showed significantly increased blood pressures and lowered heart rate with elastic fiber disruption and increased expressions of Bmal1,cyclin B1 and CDK1 in the thoracic aorta(P<0.05).In cultured RTAECs,heat stress caused significant increase of Bmal1,cyclin B1 and CDK1 protein expression levels,which were obviously lowered in cells with prior si-Bmal1 transfection.Bmal1 knockdown also inhibited heat stress-induced increase of apoptosis in RTAECs as evidenced by decreased expression of Bax and increased expression of Bcl-2.Conclusion Heat stress upregulates Bmal1 expression and causes alterations in expressions of cyclins to trigger apoptosis of rat thoracic aorta endothelial cells,which can be partly alleviated by suppressing Bmal1 expression.展开更多
Liver diseases are progressive conditions driven by multiple factors,including molecular regulators such as nonprotein-coding RNAs,which orchestrate genetic and epigenetic processes across various biological levels.Lo...Liver diseases are progressive conditions driven by multiple factors,including molecular regulators such as nonprotein-coding RNAs,which orchestrate genetic and epigenetic processes across various biological levels.Long noncoding RNAs(lncRNAs),RNA molecules longer than 200 nucleotides,have been identified as key modulators in both cancerous and noncancerous liver diseases.Among them,taurine-upregulated gene 1(TUG1),one of the earliest discovered lncRNAs,has emerged as a tumor promoter in hepatocellular carcinoma.Functionally,TUG1 exerts its regulatory effects primarily through microRNA sponging as a competing endogenous RNA while also exhibiting protein-binding capabilities that suggest additional roles in both transcriptional and posttranscriptional regulation.Furthermore,evidence suggests that dysregulation of TUG1 is closely linked to the development and progression of liver diseases.This review explores the key characteristics,mechanisms,and signaling pathways through which TUG1 affects liver disease,offering fresh insights into potential therapeutic directions and new avenues for future TUG1-related research.展开更多
Maize(Zea mays L.)is a globally significant crop essential for food,feed,and bioenergy production.The maize kernel,serving as a primary sink for starch,proteins,lipids,and essential micronutrients,is crucial for enhan...Maize(Zea mays L.)is a globally significant crop essential for food,feed,and bioenergy production.The maize kernel,serving as a primary sink for starch,proteins,lipids,and essential micronutrients,is crucial for enhancing maize yield and quality.Previous studies have established the critical role of Polycomb Repressive Complex 2(PRC2)in regulating kernel development.In this study,we applied a reverse genetics approach to investigate the role of ZmFIE1,the homolog of the PRC2 complex component Extra sex combs(Esc),in maize development.The functional loss of ZmFIE1 significantly reduces embryo size in the early stage but has a relatively small impact on mature kernels.Integrating transcriptional and metabolomic profiling suggests that ZmFIE1 is involved in regulating nutrient balance between the endosperm and embryo.In addition,we demonstrate that ZmFIE1 is maternally expressed,and that the maternal inheritance of the fie1 allele significantly affects the imprinting status of paternally imprinted genes.Overall,our results suggest that ZmFIE1 is a key gene involved in the modulation of embryo development via regulating genomic imprinting and nutrient balance between embryo and endosperm,which provides new insights into the regulation mechanism underlying kernel development.展开更多
Flight feathers represent a hallmark innovation of avian evolution.Recent comparative genomic analyses identified a 284 bp avian-specific highly conserved element(ASHCE)located within the eighth intron of the SIM bHLH...Flight feathers represent a hallmark innovation of avian evolution.Recent comparative genomic analyses identified a 284 bp avian-specific highly conserved element(ASHCE)located within the eighth intron of the SIM bHLH transcription factor 1(Sim1)gene,postulated to act as a cis-regulatory element governing flight feather morphogenesis.To investigate its functional significance,genome-edited(GE)primordial germ cell(PGC)lines carrying targeted ASHCE deletions were generated using CRISPR/Cas9-mediated editing,with germline chimeric males subsequently mated with wild-type(WT)hens to obtain GE progeny.The resulting GE chickens harbored 257-260 bp deletions,excising approximately half of the Sim1-ASHCE sequence.Reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR)analysis showed an average 0.32-fold reduction in Sim1 expression in the forelimbs of GE embryos at day 8(E8)compared to WT counterparts.Despite this,GE chickens developed structurally normal flight and tail feathers.In situ hybridization localized Sim1 expression to the posterior mesenchyme surrounding flight feather buds in E8 WT embryos,but not within the buds themselves.These results suggest that partial deletion of Sim1-ASHCE,despite diminishing Sim1 expression,does not disrupt flight feather formation.The excised region appears to possess enhancer activity toward Sim1 but is dispensable for flight feather development.Complete ablation of the ASHCE will be necessary to fully resolve the regulatory role of Sim1 in avian feather morphogenesis.展开更多
BACKGROUND Wolfram syndrome is a rare autosomal recessive genetic disorder characterized by early-onset diabetes and progressive neurodegeneration,most notably sensorineural hearing loss and optic atrophy.Because its ...BACKGROUND Wolfram syndrome is a rare autosomal recessive genetic disorder characterized by early-onset diabetes and progressive neurodegeneration,most notably sensorineural hearing loss and optic atrophy.Because its initial manifestations are usually similar to those of type 1 diabetes,the diagnosis may be delayed until other manifestations appear.Pathogenic variations of the WFS1 gene can disrupt endoplasmic reticulum function and cellular homeostasis,but the complete mutation spectrum of WFS1 has not been fully determined.Early identification of monogenic diabetes caused by Wolfram syndrome is of vital importance,as it enables the provision of targeted multidisciplinary care and genetic counseling for affected families.CASE SUMMARY A 2-year-old Han Chinese girl was admitted with a 1-month history of polydipsia,polyuria,and polyphagia,and was diagnosed with diabetic ketoacidosis and impaired insulin secretion.Sensorineural hearing loss was also detected.Wholeexome sequencing identified a previously unreported heterozygous mutation,WFS1 c.986T>C(p.Phe329Ser),in the patient and her father,confirming the diagnosis of Wolfram syndrome.Bioinformatic analysis supported the likely pathogenicity of this mutation.In silico pathogenicity predictors(REVEL,SIFT,Poly-Phen-2,MutationTaster,and GERP+)supported a deleterious effect on wolframin structure and function.The patient was initially treated with intravenous insulin and fluid resuscitation,then transitioned to a basal–bolus insulin regimen.Glycemic control was subsequently maintained with continuous subcutaneous insulin infusion and intermittent subcutaneous injections.At the 1-and 6-month follow-ups,blood glucose remained well controlled(hemoglobin A1c:5.89%and 6.58%,respectively),with no evidence of organ dysfunction or further complications.CONCLUSION This case identifies WFS1 c.986T>C(p.Phe329Ser)as a novel pathogenic variant causing Wolfram syndrome.It highlights the importance of early genetic testing in pediatric patients with atypical diabetes presentations to enable timely diagnosis,individualized therapy,and comprehensive family support.展开更多
BACKGROUND Dystrophic epidermolysis bullosa is characterized by fragile ulcerations of the skin caused by mutations in specific genes.However,genetic typing of this con-dition is rare.CASE SUMMARY An 11-year-old femal...BACKGROUND Dystrophic epidermolysis bullosa is characterized by fragile ulcerations of the skin caused by mutations in specific genes.However,genetic typing of this con-dition is rare.CASE SUMMARY An 11-year-old female suffered from recurrent fever,visible ulcerations of the entire skin,and severe malnutrition.Genetic testing revealed a frameshift mu-tation in the coding region 4047 of the 35th intron region of COL7A1,and she was diagnosed as malnutrition-type epidermolysis bullosa.Drug therapy(immu-noglobulin,fresh frozen plasma),topical therapy(silver ion dressing),fever redu-ction,cough relief,and promotion of gastrointestinal peristalsis are mainly used for respiratory and gastrointestinal complications.The patient’s condition impro-ved after treatment.CONCLUSION Dystrophic epidermolysis bullosa caused by a new framework shift mutation in COL7A1 should be taken seriously.展开更多
目的探讨Ⅰ型神经纤维瘤病(NF1)基因变异合并细胞周期蛋白依赖性激酶13(CDK13)基因变异患儿的临床特征和遗传学特点。方法收集1例NF1合并CDK13相关疾病患儿的临床资料,对患儿及其父母进行全外显子组测序,采用Sanger测序验证可疑变异,并...目的探讨Ⅰ型神经纤维瘤病(NF1)基因变异合并细胞周期蛋白依赖性激酶13(CDK13)基因变异患儿的临床特征和遗传学特点。方法收集1例NF1合并CDK13相关疾病患儿的临床资料,对患儿及其父母进行全外显子组测序,采用Sanger测序验证可疑变异,并进行家系分析。以“CDK13基因和NF1基因”或“CDK13 gene and NF1 gene”为检索词分别检索中国知网、万方数据知识服务平台和PubMed数据库建库至2024年2月的相关文献,总结同患NF1和CDK13相关疾病患者的临床表型和遗传学特征。结果患儿,男,13岁,主要临床表现为皮肤牛奶咖啡斑,矮小身材,特殊面容(上眼睑外斜、宽眼距、内眦赘皮、鼻梁宽),智力障碍。患儿存在NF1基因杂合变异c.3610C>G(p.Arg1204Gly)和CDK13基因移码突变c.484dupG(p.Ala162Glyfs*108)(杂合)。Sanger测序验证结果显示,患儿母亲携带NF1基因杂合变异,未携带CDK13基因移码突变;父亲均未携带。未检索到关于同患NF1和CDK13相关疾病的患者的文献。共检索到CDK13相关疾病文献11篇,文献复习结果显示,97例患者主要临床表现为智力障碍或发育迟缓、特殊面容、先天性心脏缺陷,致病变异以错义突变为主。结论NF1基因变异可导致NF1。当发现有特殊面容的NF1患儿出现无法解释的现有表型或症状时,应注意2种遗传病同时存在的可能性。展开更多
基金funded by the National Key Research and Development Program of China(Grant No.2022YFF1003100)Modern Citrus Industry Technology System of China(Grant No.CARS-26).
文摘Polyembryony has posed a significant impediment to the advancement of citrus hybrid breeding.FhRWP is widely regarded as a pivotal factor governing asexual reproduction in citrus,and prior research has demonstrated that FhARID1,acting as an upstream regulator,modulates FhRWP expression.In this study,we performed a genome-wide characterization of the ARID-HMG-related genes using the short juvenile minicitrus Fortunella hindsii.A total of 20 ARID-HMG-related genes were identified.Protein interaction network and enrichment analysis suggested that ARID-HMG-related proteins might might be involved in chromatin remodeling complexes.Knockout of FhARID1 in F.hindsii did not induce the conversion from polyembryony to monoembryony.However,fharid1 plants in T1 generation exhibited abnormal proliferation at axillary buds,which is similar to phenotype of fhrwp plants.Expression analysis of fharid1 ovary tissues revealed the downregulation of FhRWP.The results indicated that FhARID1,as an upstream regulator of FhRWP,has an effect on the development of citrus axillary buds.Expression analysis of overexpressed leaves of FhARID1 lines showed that no significant up-regulation of FhRWP,indicating that FhARID1 is not the sole upstream regulatory factor of FhRWP.Only FhARID2 showed a correlation in expression with FhARID1 among the ARID-related genes,further supporting the notion that this gene may be involved in complex formation rather than acting alone.Yeast two-hybrid and MS/MS spectra further indicated that FhARID1 function requires casein kinase II-mediated post-transcriptional phosphorylation.This study elucidated the function of FhARID1 in citrus apomixis and axillary bud development,providing a fundamental basis for understanding the role of ARID-HMG-related genes.
基金supported by the National Natural Science Foundation of China,Nos.82071008(to BL)and 82004001(to XJ)Medical Science and Technology Program of Health Commission of Henan Province,No.LHGJ20210072(to RQ)Science and Technology Department of Henan Province,No.212102310307(to XJ)。
文摘Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.
文摘Objective To investigate the structural changes of rat thoracic aorta and changes in expression levels of Bmal1 and cyclins in thoracic aorta endothelial cells following heat stress.Methods Twenty male SD rats were randomized equally into control group and heat stress group.After exposure to 32℃for 2 weeks in the latter group,the rats were examined for histopathological changes and Bmal1 expression in the thoracic aorta using HE staining and immunohistochemistry.In the cell experiments,cultured rat thoracic aortic endothelial cells(RTAECs)were incubated at 40℃for 12 h with or without prior transfection with a Bmal1-specific small interfering RNA(si-Bmal1)or a negative sequence.In both rat thoracic aorta and RTAECs,the expressions of Bmal1,the cell cycle proteins CDK1,CDK4,CDK6,and cyclin B1,and apoptosis-related proteins Bax and Bcl-2 were detected using Western blotting.TUNEL staining was used to detect cell apoptosis in rat thoracic aorta,and the changes in cell cycle distribution and apoptosis in RTAECs were analyzed with flow cytometry.Results Compared with the control rats,the rats exposed to heat stress showed significantly increased blood pressures and lowered heart rate with elastic fiber disruption and increased expressions of Bmal1,cyclin B1 and CDK1 in the thoracic aorta(P<0.05).In cultured RTAECs,heat stress caused significant increase of Bmal1,cyclin B1 and CDK1 protein expression levels,which were obviously lowered in cells with prior si-Bmal1 transfection.Bmal1 knockdown also inhibited heat stress-induced increase of apoptosis in RTAECs as evidenced by decreased expression of Bax and increased expression of Bcl-2.Conclusion Heat stress upregulates Bmal1 expression and causes alterations in expressions of cyclins to trigger apoptosis of rat thoracic aorta endothelial cells,which can be partly alleviated by suppressing Bmal1 expression.
文摘Liver diseases are progressive conditions driven by multiple factors,including molecular regulators such as nonprotein-coding RNAs,which orchestrate genetic and epigenetic processes across various biological levels.Long noncoding RNAs(lncRNAs),RNA molecules longer than 200 nucleotides,have been identified as key modulators in both cancerous and noncancerous liver diseases.Among them,taurine-upregulated gene 1(TUG1),one of the earliest discovered lncRNAs,has emerged as a tumor promoter in hepatocellular carcinoma.Functionally,TUG1 exerts its regulatory effects primarily through microRNA sponging as a competing endogenous RNA while also exhibiting protein-binding capabilities that suggest additional roles in both transcriptional and posttranscriptional regulation.Furthermore,evidence suggests that dysregulation of TUG1 is closely linked to the development and progression of liver diseases.This review explores the key characteristics,mechanisms,and signaling pathways through which TUG1 affects liver disease,offering fresh insights into potential therapeutic directions and new avenues for future TUG1-related research.
基金supported by STI2030-Major Projects(2023ZD04069,Z231100003723004)the National Science Fund for Distinguished Young Scholars(32425041)the Chinese Universities Scientific Fund(2024TC165).
文摘Maize(Zea mays L.)is a globally significant crop essential for food,feed,and bioenergy production.The maize kernel,serving as a primary sink for starch,proteins,lipids,and essential micronutrients,is crucial for enhancing maize yield and quality.Previous studies have established the critical role of Polycomb Repressive Complex 2(PRC2)in regulating kernel development.In this study,we applied a reverse genetics approach to investigate the role of ZmFIE1,the homolog of the PRC2 complex component Extra sex combs(Esc),in maize development.The functional loss of ZmFIE1 significantly reduces embryo size in the early stage but has a relatively small impact on mature kernels.Integrating transcriptional and metabolomic profiling suggests that ZmFIE1 is involved in regulating nutrient balance between the endosperm and embryo.In addition,we demonstrate that ZmFIE1 is maternally expressed,and that the maternal inheritance of the fie1 allele significantly affects the imprinting status of paternally imprinted genes.Overall,our results suggest that ZmFIE1 is a key gene involved in the modulation of embryo development via regulating genomic imprinting and nutrient balance between embryo and endosperm,which provides new insights into the regulation mechanism underlying kernel development.
基金supported by the Ministry of Agriculture and Rural Affairs of the People's Republic of China(125A0607)Department of Science and Technology of Yunnan Province(XDYC-KJLJ-2022-0004)。
文摘Flight feathers represent a hallmark innovation of avian evolution.Recent comparative genomic analyses identified a 284 bp avian-specific highly conserved element(ASHCE)located within the eighth intron of the SIM bHLH transcription factor 1(Sim1)gene,postulated to act as a cis-regulatory element governing flight feather morphogenesis.To investigate its functional significance,genome-edited(GE)primordial germ cell(PGC)lines carrying targeted ASHCE deletions were generated using CRISPR/Cas9-mediated editing,with germline chimeric males subsequently mated with wild-type(WT)hens to obtain GE progeny.The resulting GE chickens harbored 257-260 bp deletions,excising approximately half of the Sim1-ASHCE sequence.Reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR)analysis showed an average 0.32-fold reduction in Sim1 expression in the forelimbs of GE embryos at day 8(E8)compared to WT counterparts.Despite this,GE chickens developed structurally normal flight and tail feathers.In situ hybridization localized Sim1 expression to the posterior mesenchyme surrounding flight feather buds in E8 WT embryos,but not within the buds themselves.These results suggest that partial deletion of Sim1-ASHCE,despite diminishing Sim1 expression,does not disrupt flight feather formation.The excised region appears to possess enhancer activity toward Sim1 but is dispensable for flight feather development.Complete ablation of the ASHCE will be necessary to fully resolve the regulatory role of Sim1 in avian feather morphogenesis.
基金Supported by Beijing Holistic Integrative Medicine Association Clinical Research Funding Program,No.ZHKY-2024-2209.
文摘BACKGROUND Wolfram syndrome is a rare autosomal recessive genetic disorder characterized by early-onset diabetes and progressive neurodegeneration,most notably sensorineural hearing loss and optic atrophy.Because its initial manifestations are usually similar to those of type 1 diabetes,the diagnosis may be delayed until other manifestations appear.Pathogenic variations of the WFS1 gene can disrupt endoplasmic reticulum function and cellular homeostasis,but the complete mutation spectrum of WFS1 has not been fully determined.Early identification of monogenic diabetes caused by Wolfram syndrome is of vital importance,as it enables the provision of targeted multidisciplinary care and genetic counseling for affected families.CASE SUMMARY A 2-year-old Han Chinese girl was admitted with a 1-month history of polydipsia,polyuria,and polyphagia,and was diagnosed with diabetic ketoacidosis and impaired insulin secretion.Sensorineural hearing loss was also detected.Wholeexome sequencing identified a previously unreported heterozygous mutation,WFS1 c.986T>C(p.Phe329Ser),in the patient and her father,confirming the diagnosis of Wolfram syndrome.Bioinformatic analysis supported the likely pathogenicity of this mutation.In silico pathogenicity predictors(REVEL,SIFT,Poly-Phen-2,MutationTaster,and GERP+)supported a deleterious effect on wolframin structure and function.The patient was initially treated with intravenous insulin and fluid resuscitation,then transitioned to a basal–bolus insulin regimen.Glycemic control was subsequently maintained with continuous subcutaneous insulin infusion and intermittent subcutaneous injections.At the 1-and 6-month follow-ups,blood glucose remained well controlled(hemoglobin A1c:5.89%and 6.58%,respectively),with no evidence of organ dysfunction or further complications.CONCLUSION This case identifies WFS1 c.986T>C(p.Phe329Ser)as a novel pathogenic variant causing Wolfram syndrome.It highlights the importance of early genetic testing in pediatric patients with atypical diabetes presentations to enable timely diagnosis,individualized therapy,and comprehensive family support.
文摘BACKGROUND Dystrophic epidermolysis bullosa is characterized by fragile ulcerations of the skin caused by mutations in specific genes.However,genetic typing of this con-dition is rare.CASE SUMMARY An 11-year-old female suffered from recurrent fever,visible ulcerations of the entire skin,and severe malnutrition.Genetic testing revealed a frameshift mu-tation in the coding region 4047 of the 35th intron region of COL7A1,and she was diagnosed as malnutrition-type epidermolysis bullosa.Drug therapy(immu-noglobulin,fresh frozen plasma),topical therapy(silver ion dressing),fever redu-ction,cough relief,and promotion of gastrointestinal peristalsis are mainly used for respiratory and gastrointestinal complications.The patient’s condition impro-ved after treatment.CONCLUSION Dystrophic epidermolysis bullosa caused by a new framework shift mutation in COL7A1 should be taken seriously.
文摘目的探讨Ⅰ型神经纤维瘤病(NF1)基因变异合并细胞周期蛋白依赖性激酶13(CDK13)基因变异患儿的临床特征和遗传学特点。方法收集1例NF1合并CDK13相关疾病患儿的临床资料,对患儿及其父母进行全外显子组测序,采用Sanger测序验证可疑变异,并进行家系分析。以“CDK13基因和NF1基因”或“CDK13 gene and NF1 gene”为检索词分别检索中国知网、万方数据知识服务平台和PubMed数据库建库至2024年2月的相关文献,总结同患NF1和CDK13相关疾病患者的临床表型和遗传学特征。结果患儿,男,13岁,主要临床表现为皮肤牛奶咖啡斑,矮小身材,特殊面容(上眼睑外斜、宽眼距、内眦赘皮、鼻梁宽),智力障碍。患儿存在NF1基因杂合变异c.3610C>G(p.Arg1204Gly)和CDK13基因移码突变c.484dupG(p.Ala162Glyfs*108)(杂合)。Sanger测序验证结果显示,患儿母亲携带NF1基因杂合变异,未携带CDK13基因移码突变;父亲均未携带。未检索到关于同患NF1和CDK13相关疾病的患者的文献。共检索到CDK13相关疾病文献11篇,文献复习结果显示,97例患者主要临床表现为智力障碍或发育迟缓、特殊面容、先天性心脏缺陷,致病变异以错义突变为主。结论NF1基因变异可导致NF1。当发现有特殊面容的NF1患儿出现无法解释的现有表型或症状时,应注意2种遗传病同时存在的可能性。
