Neurofibromatosis type I（NF1） is a hereditary,autosomal dominant,neurocutaneous syndrome that is attributed to NF1 gene mutation.NF1 has been associated with scoliosis,macrocephaly,pseudoarthrosis,short stature,ment...Neurofibromatosis type I（NF1） is a hereditary,autosomal dominant,neurocutaneous syndrome that is attributed to NF1 gene mutation.NF1 has been associated with scoliosis,macrocephaly,pseudoarthrosis,short stature,mental retardation,and malignancies.NF1-associated vasculopathy is an uncommon and easily-overlooked presentation.Examination of a Chinese family affected by NF1 combined with cerebral vessel stenosis and/ or abnormality suggested a possible relationship between NF1 and vessel stenosis.To determine which NF1 gene mutation is associated with vascular lesions,particularly cerebral vessel stenosis,we examined one rare family with combined cerebral vessel lesions or maldevelopment.Vascular lesions were detected using transcranial Doppler sonography and digital subtraction angiography in family members.Next,denaturing high-performance liquid chromatography and sequencing were used to screen for NF1 gene mutations.The results revealed a nonsense mutation,c.541C＆gt;T,in the NF1 gene.This mutation truncated the NF1 protein by 2659 aminoacid residues at the C-terminus and co-segregated with all of the patients,but was not present in unaffected individuals in the family.Exceptionally,three novel mutations were identified in unaffected family members,but these did not affect the product of the NF1 gene.Thus the nonsense mutation,c.541C＆gt;T,located in the NF1 gene could constitute one genetic factor for cerebral vessel lesions.展开更多
Objective Poly（rC）-binding protein 1 （PCBP1） belongs to the heterogeneous nuclear ribonucleoprotein family and participates in transcriptional and translational regulation. Previous work has identified transcripts...Objective Poly（rC）-binding protein 1 （PCBP1） belongs to the heterogeneous nuclear ribonucleoprotein family and participates in transcriptional and translational regulation. Previous work has identified transcripts targeted by both knockdown and overexpression of PCBP1 in SH-SY5Y neuroblastoma cells using a microarray or ProteomeLabTM protein fractionation 2-dimensions （PF-2D） and quadrupole time-of-flight mass spectrometer. The present study aimed to further determine whether these altered transcripts from major pathways （such as Wnt signaling, TGF-β signaling, cell cycling, and apoptosis） and two other genes, H2AFX and H2BFS （screened by PF-2D）, have spatial relationships. Methods The genes were studied by qRT-PCR, and dynamic Bayesian network analysis was used to rebuild the coordination network of these transcripts. Results PCBP1 controlled the expression or activity of the seven transcripts. Moreover, PCBP1 indirectly regulated MAP2K2, FOS, FST, TP53 and WNT7B through H2AFX or regulated these genes through SAT. In contrast, TP53 and WNT7B are regulated by other genes. Conclusion The seven transcripts and PCBP1 are closely associated in a spatial interaction network.展开更多
基金supported by the National High Technology Development Project(863 Project)of China(2006AA02Z497)the National Basic Research Development Program(973 program)of China(2007CB511902)the National Natural Science Foundation of China(81341036)
文摘Neurofibromatosis type I（NF1） is a hereditary,autosomal dominant,neurocutaneous syndrome that is attributed to NF1 gene mutation.NF1 has been associated with scoliosis,macrocephaly,pseudoarthrosis,short stature,mental retardation,and malignancies.NF1-associated vasculopathy is an uncommon and easily-overlooked presentation.Examination of a Chinese family affected by NF1 combined with cerebral vessel stenosis and/ or abnormality suggested a possible relationship between NF1 and vessel stenosis.To determine which NF1 gene mutation is associated with vascular lesions,particularly cerebral vessel stenosis,we examined one rare family with combined cerebral vessel lesions or maldevelopment.Vascular lesions were detected using transcranial Doppler sonography and digital subtraction angiography in family members.Next,denaturing high-performance liquid chromatography and sequencing were used to screen for NF1 gene mutations.The results revealed a nonsense mutation,c.541C＆gt;T,in the NF1 gene.This mutation truncated the NF1 protein by 2659 aminoacid residues at the C-terminus and co-segregated with all of the patients,but was not present in unaffected individuals in the family.Exceptionally,three novel mutations were identified in unaffected family members,but these did not affect the product of the NF1 gene.Thus the nonsense mutation,c.541C＆gt;T,located in the NF1 gene could constitute one genetic factor for cerebral vessel lesions.
基金supported in part by the National Basic Research Program of China (2011CB504100)the National Natural Science Foundation of China (81072858)the "973" project(2007CB511902) from the Ministry of Science and Technology of the People’s Republic of China
文摘Objective Poly（rC）-binding protein 1 （PCBP1） belongs to the heterogeneous nuclear ribonucleoprotein family and participates in transcriptional and translational regulation. Previous work has identified transcripts targeted by both knockdown and overexpression of PCBP1 in SH-SY5Y neuroblastoma cells using a microarray or ProteomeLabTM protein fractionation 2-dimensions （PF-2D） and quadrupole time-of-flight mass spectrometer. The present study aimed to further determine whether these altered transcripts from major pathways （such as Wnt signaling, TGF-β signaling, cell cycling, and apoptosis） and two other genes, H2AFX and H2BFS （screened by PF-2D）, have spatial relationships. Methods The genes were studied by qRT-PCR, and dynamic Bayesian network analysis was used to rebuild the coordination network of these transcripts. Results PCBP1 controlled the expression or activity of the seven transcripts. Moreover, PCBP1 indirectly regulated MAP2K2, FOS, FST, TP53 and WNT7B through H2AFX or regulated these genes through SAT. In contrast, TP53 and WNT7B are regulated by other genes. Conclusion The seven transcripts and PCBP1 are closely associated in a spatial interaction network.
