Helsmoortel-Van der Aa综合征(HVDAS)是一种罕见的神经发育障碍性疾病,主要由活性依赖性神经保护蛋白(ADNP)基因突变引起,是最常见的孤独症谱系障碍(ASD)单基因病因之一。本文分析2024年就诊于海口市妇幼保健院的1例患儿,男,3岁10个月...Helsmoortel-Van der Aa综合征(HVDAS)是一种罕见的神经发育障碍性疾病,主要由活性依赖性神经保护蛋白(ADNP)基因突变引起,是最常见的孤独症谱系障碍(ASD)单基因病因之一。本文分析2024年就诊于海口市妇幼保健院的1例患儿,男,3岁10个月,因“运动、语言发育迟缓2年余,社交障碍1年余”入院,检查发现患儿存在孤独症谱系障碍、全面发育迟缓、特殊面容、矮小、脑积水等临床表现,基因检测发现患儿携带ADNP基因杂合突变{NM_001282531.3(ADNP):c.2189(exon6)delG[p.(Arg730Glnfs3)]},其父母及妹妹均未携带该突变。总结临床资料并结合文献复习,ADNP基因在染色质重塑和神经发育障碍中发挥重要作用,ADNP基因突变可累及多系统。此例HVDAS具有典型临床表现,并拓宽了脑积水的表型谱,为此类基因变异的遗传咨询以及临床医师的早期识别提供了参考依据。展开更多
Background:Allergic eosinophilic asthma(EA)and eosinophilic granulomatosis with polyangiitis(EGPA)share significant overlaps in both epidemiology and pathogenesis,suggesting a potential link between the two con-dition...Background:Allergic eosinophilic asthma(EA)and eosinophilic granulomatosis with polyangiitis(EGPA)share significant overlaps in both epidemiology and pathogenesis,suggesting a potential link between the two con-ditions.Despite these associations,the underlying molecular and cellular mechanisms driving their connection remain poorly understood.Methods:We retrieved GSE143303 of EA and GSE144302 of EGPA from the GEO database and conducted dif-ferential expression analysis as well as functional enrichment analysis to identify differentially expressed genes(DEGs)and potential pathogenic pathways.A protein-protein interaction(PPI)network was generated using the STRING database.Key hub genes were determined through cytoHubba.We added two publicly reported EA and EGPA-related transcriptome datasets,GSE117038 and GSE119136,for mutual verification.Subsequent valida-tion was performed via immune infiltration assessment utilizing CIBERSORT.Results:In total,267 DEGs were identified,in which HSP90AA1,HSPA8,CCND1,RPS20,CD74,RPL5,RPS6,RHOA,RPS3A and FLT3LG are the top 10 hub genes,while the antigen processing and presentation pathway and leukocyte cell-cell adhesion pathway were the potential influential pathways.Increased naïve B cells and M1 type of Macrophages were detected in EA patients through immune infiltration analysis.Conclusions:Utilizing bioinformatics techniques,this study is the initial investigation to uncover the shared mechanisms involving the antigen processing and presentation pathway and leukocyte adhesion pathways in the progression of both EA and EGPA.It may offer potential biomarkers for future studies on the underlying path-ogenesis and treatment of EA and EGPA as well as eosinophilia related co-morbidities.展开更多
目的:通过高通量转录组测序和相对定量血清蛋白组学技术筛选肝癌转移相关的关键基因.方法:利用Ion Proton.测序仪比较人肝癌细胞株(Smmc-7721)和正常人肝细胞株(L-02)的差异表达基因,对差异表达基因进行聚类分析、GO功能注释和富集分析...目的:通过高通量转录组测序和相对定量血清蛋白组学技术筛选肝癌转移相关的关键基因.方法:利用Ion Proton.测序仪比较人肝癌细胞株(Smmc-7721)和正常人肝细胞株(L-02)的差异表达基因,对差异表达基因进行聚类分析、GO功能注释和富集分析,获得肝癌细胞转移相关基因;收集10例肝细胞癌(hepatocellular carcinoma,HCC)患者血清及匹配10例正常人血清,通过相对和绝对定量的同位素标记(isobaric tags for relative and absolute quantitation,iTRAQ)联合基质辅助激光解吸电离串联飞行时间质谱(ma t r ixassisted laser desorption/ionization tandemtime of flight mass spectrometry,MALDITOF/MS)检测肝癌与正常对照组血清差异表达蛋白;将两组学结果进行交集分析,确定肝癌转移关键基因,并在76例HCC和癌旁组织中进行免疫组织化学验证.结果:对肝癌细胞及正常肝细胞进行转录组测序分析,共得到肝癌细胞差异表达基因618个,生物信息学分析差异表达基因主要聚集在转移相关、转录因子相关、氧化还原过程等14个分子功能,其中转移相关功能基因所占比例最大,达15.05%(93/618);血清蛋白组学分析共得到69个肝癌血清差异表达蛋白,其中在肝癌组上调33个,下调36个;将转录组测序筛选的与转移功能相关基因与蛋白质组学进行交集分析,发现有3个共同交集的差异因子,其中差异最明显的是肝癌中表达上调的热休克蛋白90 AA1(heat shock protein 90 AA1,HSP90AA1);免疫组织化学验证结果显示,HSP90α表达强阳性在门脉转移和无门脉转移HCC组织中的比例分别为66.7%(16/24)和25%(13/52)(P<0.005),HSP90α在有门脉转移的肝癌组织表达明显增高.结论:利用转录组结合血清蛋白组策略,发现HSP90AA1可能是在肝癌转移重要基因.展开更多
文摘Helsmoortel-Van der Aa综合征(HVDAS)是一种罕见的神经发育障碍性疾病,主要由活性依赖性神经保护蛋白(ADNP)基因突变引起,是最常见的孤独症谱系障碍(ASD)单基因病因之一。本文分析2024年就诊于海口市妇幼保健院的1例患儿,男,3岁10个月,因“运动、语言发育迟缓2年余,社交障碍1年余”入院,检查发现患儿存在孤独症谱系障碍、全面发育迟缓、特殊面容、矮小、脑积水等临床表现,基因检测发现患儿携带ADNP基因杂合突变{NM_001282531.3(ADNP):c.2189(exon6)delG[p.(Arg730Glnfs3)]},其父母及妹妹均未携带该突变。总结临床资料并结合文献复习,ADNP基因在染色质重塑和神经发育障碍中发挥重要作用,ADNP基因突变可累及多系统。此例HVDAS具有典型临床表现,并拓宽了脑积水的表型谱,为此类基因变异的遗传咨询以及临床医师的早期识别提供了参考依据。
基金funded by National Natural Science Foundation of China(NO.82370083).
文摘Background:Allergic eosinophilic asthma(EA)and eosinophilic granulomatosis with polyangiitis(EGPA)share significant overlaps in both epidemiology and pathogenesis,suggesting a potential link between the two con-ditions.Despite these associations,the underlying molecular and cellular mechanisms driving their connection remain poorly understood.Methods:We retrieved GSE143303 of EA and GSE144302 of EGPA from the GEO database and conducted dif-ferential expression analysis as well as functional enrichment analysis to identify differentially expressed genes(DEGs)and potential pathogenic pathways.A protein-protein interaction(PPI)network was generated using the STRING database.Key hub genes were determined through cytoHubba.We added two publicly reported EA and EGPA-related transcriptome datasets,GSE117038 and GSE119136,for mutual verification.Subsequent valida-tion was performed via immune infiltration assessment utilizing CIBERSORT.Results:In total,267 DEGs were identified,in which HSP90AA1,HSPA8,CCND1,RPS20,CD74,RPL5,RPS6,RHOA,RPS3A and FLT3LG are the top 10 hub genes,while the antigen processing and presentation pathway and leukocyte cell-cell adhesion pathway were the potential influential pathways.Increased naïve B cells and M1 type of Macrophages were detected in EA patients through immune infiltration analysis.Conclusions:Utilizing bioinformatics techniques,this study is the initial investigation to uncover the shared mechanisms involving the antigen processing and presentation pathway and leukocyte adhesion pathways in the progression of both EA and EGPA.It may offer potential biomarkers for future studies on the underlying path-ogenesis and treatment of EA and EGPA as well as eosinophilia related co-morbidities.
文摘目的:通过高通量转录组测序和相对定量血清蛋白组学技术筛选肝癌转移相关的关键基因.方法:利用Ion Proton.测序仪比较人肝癌细胞株(Smmc-7721)和正常人肝细胞株(L-02)的差异表达基因,对差异表达基因进行聚类分析、GO功能注释和富集分析,获得肝癌细胞转移相关基因;收集10例肝细胞癌(hepatocellular carcinoma,HCC)患者血清及匹配10例正常人血清,通过相对和绝对定量的同位素标记(isobaric tags for relative and absolute quantitation,iTRAQ)联合基质辅助激光解吸电离串联飞行时间质谱(ma t r ixassisted laser desorption/ionization tandemtime of flight mass spectrometry,MALDITOF/MS)检测肝癌与正常对照组血清差异表达蛋白;将两组学结果进行交集分析,确定肝癌转移关键基因,并在76例HCC和癌旁组织中进行免疫组织化学验证.结果:对肝癌细胞及正常肝细胞进行转录组测序分析,共得到肝癌细胞差异表达基因618个,生物信息学分析差异表达基因主要聚集在转移相关、转录因子相关、氧化还原过程等14个分子功能,其中转移相关功能基因所占比例最大,达15.05%(93/618);血清蛋白组学分析共得到69个肝癌血清差异表达蛋白,其中在肝癌组上调33个,下调36个;将转录组测序筛选的与转移功能相关基因与蛋白质组学进行交集分析,发现有3个共同交集的差异因子,其中差异最明显的是肝癌中表达上调的热休克蛋白90 AA1(heat shock protein 90 AA1,HSP90AA1);免疫组织化学验证结果显示,HSP90α表达强阳性在门脉转移和无门脉转移HCC组织中的比例分别为66.7%(16/24)和25%(13/52)(P<0.005),HSP90α在有门脉转移的肝癌组织表达明显增高.结论:利用转录组结合血清蛋白组策略,发现HSP90AA1可能是在肝癌转移重要基因.
