目的探讨LMNA相关的先天性肌营养不良症的临床特征和诊断。方法回顾1例LMNA基因突变引起的肌营养不良症病例的临床资料,并复习相关文献。结果患儿,女,8个月,临床表现为抬头乏力、眼睑下垂、运动发育迟缓。检测患儿及其父母、姐姐的LMNA...目的探讨LMNA相关的先天性肌营养不良症的临床特征和诊断。方法回顾1例LMNA基因突变引起的肌营养不良症病例的临床资料,并复习相关文献。结果患儿,女,8个月,临床表现为抬头乏力、眼睑下垂、运动发育迟缓。检测患儿及其父母、姐姐的LMNA基因,显示患儿存在杂合突变c.94-96 del AAG(p.K32del),确诊为LMNA突变引起的肌营养不良。患儿父母及姐姐均未发现LMNA基因突变。文献检索显示,LMNA相关的先天性肌营养不良症患儿80%以上以抬头乏力为主要表现,并且可能交叉重叠存在肢体近端肌无力、运动发育迟缓、轴向肌无力。结论 LMNA基因分析有助于早期诊断先天性肌营养不良。展开更多
Objective: To intensively investigate sporadic CMT patients, we have analyzed the LMNA gene in this study in a series of 32 unrelated CMT patients. Methods: Twelve exons of the LMNA gene were amplified from genetomic ...Objective: To intensively investigate sporadic CMT patients, we have analyzed the LMNA gene in this study in a series of 32 unrelated CMT patients. Methods: Twelve exons of the LMNA gene were amplified from genetomic DNA. PCR products of each exon were analyzed by single strand conformational polymorphism (SSCP). Results: No abnormal SSCP pattern, suggesting no mutation in our CMT patients, was detected. Conclusion: The CMT diseases resulted from the mutations of LMNA gene were rare.展开更多
目的研究敲减LMNA基因(编码lamin A/C)对肾癌细胞786-O的基因表达谱的影响,从而探讨LMNA在肾癌发生发展中的分子机制。方法在完全培养基RPMI 1640中培养肾癌细胞系786-O,将siRNA(siControl、siLMNA-2)转染786-O细胞,72 h后收集细胞,提取...目的研究敲减LMNA基因(编码lamin A/C)对肾癌细胞786-O的基因表达谱的影响,从而探讨LMNA在肾癌发生发展中的分子机制。方法在完全培养基RPMI 1640中培养肾癌细胞系786-O,将siRNA(siControl、siLMNA-2)转染786-O细胞,72 h后收集细胞,提取RNA,建立cDNA文库并利用Illumina测序平台进行RNA测序(RNA-seq)。测序结果经联川生物平台分析,鉴定DEGs。细胞经siControl、siLMNA-1、siLMNA-2转染后对部分基因进行实时荧光定量PCR(qPCR)验证。DEGs经Gene Ontology(GO)和Kyoto Encyclopedia of Genes and Gnomes(KEGG)富集分析,并探讨了部分DEGs在临床样本中的表达水平与总生存期(Overall survival,OS)的相关性。结果鉴定到89个DEGs,46个上调,43个下调。GO分析表明转录调控(Regulation of transcription,DNA-templated)、肽修饰(Peptide modification)、真核生物的核糖体生物发生(Ribosome biogenesis in eukaryotes)、牛磺酸和低牛磺酸代谢(Taurine and hypotaurine metabolism)等显著富集。部分受LMNA调控的DEGs如MIEF1、UTP14C、SPIN1等基因在临床标本中较低表达,并与较差的OS相关。结论LMNA基因除了编码lamin A/C作为核纤层主要成分起着核骨架的作用外,还可能通过影响MIEF1、UTP14C、SPIN1等基因的表达,参与到肾细胞癌的发生发展过程。这些基因产物有可能为临床上LMNA扩增或高表达的病人类型,提供诊断标志和潜在的药物靶标。展开更多
Laminopathies are genetic diseases that encompass a wide spectrum of phenotypes with diverse tissue pathologies and result mainly from mutations in the LMNA gene encoding nuclear lamin A/C. To date, at least 9 differe...Laminopathies are genetic diseases that encompass a wide spectrum of phenotypes with diverse tissue pathologies and result mainly from mutations in the LMNA gene encoding nuclear lamin A/C. To date, at least 9 different human diseases, which superficially seem to share little with one another, result from LMNA mutations. The position of the mutation within LMNA appears to be associated with the phenotypes. This review gives an overview of genotype-phenotype relationship and describes recent advances in animal models and pathogenic mechanisms.展开更多
文摘目的探讨LMNA相关的先天性肌营养不良症的临床特征和诊断。方法回顾1例LMNA基因突变引起的肌营养不良症病例的临床资料,并复习相关文献。结果患儿,女,8个月,临床表现为抬头乏力、眼睑下垂、运动发育迟缓。检测患儿及其父母、姐姐的LMNA基因,显示患儿存在杂合突变c.94-96 del AAG(p.K32del),确诊为LMNA突变引起的肌营养不良。患儿父母及姐姐均未发现LMNA基因突变。文献检索显示,LMNA相关的先天性肌营养不良症患儿80%以上以抬头乏力为主要表现,并且可能交叉重叠存在肢体近端肌无力、运动发育迟缓、轴向肌无力。结论 LMNA基因分析有助于早期诊断先天性肌营养不良。
文摘Objective: To intensively investigate sporadic CMT patients, we have analyzed the LMNA gene in this study in a series of 32 unrelated CMT patients. Methods: Twelve exons of the LMNA gene were amplified from genetomic DNA. PCR products of each exon were analyzed by single strand conformational polymorphism (SSCP). Results: No abnormal SSCP pattern, suggesting no mutation in our CMT patients, was detected. Conclusion: The CMT diseases resulted from the mutations of LMNA gene were rare.
文摘目的研究敲减LMNA基因(编码lamin A/C)对肾癌细胞786-O的基因表达谱的影响,从而探讨LMNA在肾癌发生发展中的分子机制。方法在完全培养基RPMI 1640中培养肾癌细胞系786-O,将siRNA(siControl、siLMNA-2)转染786-O细胞,72 h后收集细胞,提取RNA,建立cDNA文库并利用Illumina测序平台进行RNA测序(RNA-seq)。测序结果经联川生物平台分析,鉴定DEGs。细胞经siControl、siLMNA-1、siLMNA-2转染后对部分基因进行实时荧光定量PCR(qPCR)验证。DEGs经Gene Ontology(GO)和Kyoto Encyclopedia of Genes and Gnomes(KEGG)富集分析,并探讨了部分DEGs在临床样本中的表达水平与总生存期(Overall survival,OS)的相关性。结果鉴定到89个DEGs,46个上调,43个下调。GO分析表明转录调控(Regulation of transcription,DNA-templated)、肽修饰(Peptide modification)、真核生物的核糖体生物发生(Ribosome biogenesis in eukaryotes)、牛磺酸和低牛磺酸代谢(Taurine and hypotaurine metabolism)等显著富集。部分受LMNA调控的DEGs如MIEF1、UTP14C、SPIN1等基因在临床标本中较低表达,并与较差的OS相关。结论LMNA基因除了编码lamin A/C作为核纤层主要成分起着核骨架的作用外,还可能通过影响MIEF1、UTP14C、SPIN1等基因的表达,参与到肾细胞癌的发生发展过程。这些基因产物有可能为临床上LMNA扩增或高表达的病人类型,提供诊断标志和潜在的药物靶标。
文摘Laminopathies are genetic diseases that encompass a wide spectrum of phenotypes with diverse tissue pathologies and result mainly from mutations in the LMNA gene encoding nuclear lamin A/C. To date, at least 9 different human diseases, which superficially seem to share little with one another, result from LMNA mutations. The position of the mutation within LMNA appears to be associated with the phenotypes. This review gives an overview of genotype-phenotype relationship and describes recent advances in animal models and pathogenic mechanisms.
