Background Familial hypercholesterolemia （FH） is a type of dominant autosomal disease that causes high levels of plasma low-density lipoprotein cholesterol （LDL-C）. In the past years, molecular data related to FH ...Background Familial hypercholesterolemia （FH） is a type of dominant autosomal disease that causes high levels of plasma low-density lipoprotein cholesterol （LDL-C）. In the past years, molecular data related to FH were limited in China. Now, to gain more information about FH, we analyzed one proband with a severe FH phenotype as well as his relatives. Methods After the entire coding sequence and the intron-exon junctions of the low-density lipoprotein receptor （LDLR） gene were amplified using PCR, we sequenced the LDLR gene of a Chinese FH family. RT-PCR was used to detect changes in the mRNA. Results Two novel mutations were identified in the LDLR gene of this family. One, W165X, was a G〉A substitution at the third nucleotide of codon 165. The other, IVS5-1G〉A, was also a G〉A substitution at the acceptor splice site of intron 5. The most striking discovery is that the proband was heterozygous for W165X but homozygous for IVS5-1G〉A. The cDNA sequencing showed that the IVS5-1G〉A mutation caused the insertion of 10 nucleotides, namely GCTCTCACAA, between exon 5 and exon 6. Conclusions The two nucleotide variations are thought to be the FH-causing mutations because the co-segregation of the mutant allele with the phenotype of FH has been shown in this Chinese family. These data show an increase in the mutational spectrum of FH in China and verify a scarce mutational form in the LDLR gene.展开更多
Vascular endothelial growth factor （VEGF） is an angiogenic regulator that stimulates endothelial cell migration, proliferation, and angiogenesis. VEGF gene therapy is a new promising approach to induce therapeutic a...Vascular endothelial growth factor （VEGF） is an angiogenic regulator that stimulates endothelial cell migration, proliferation, and angiogenesis. VEGF gene therapy is a new promising approach to induce therapeutic angiogenesis for the treatment of ischemic myocardial and limb diseases. Recently, clinical studies have demonstrated successful outcomes using plasmids, retroviruses and adenoviruses.l-3 But the safety of those vectors is poor, which has become a serious concern. Besides immunogenicity caused by viral vectors, a further problem is that viral vectors show a preference to integrate into the transcription or control region of active genes, which may induce tumors and other disorders.展开更多
文摘Background Familial hypercholesterolemia （FH） is a type of dominant autosomal disease that causes high levels of plasma low-density lipoprotein cholesterol （LDL-C）. In the past years, molecular data related to FH were limited in China. Now, to gain more information about FH, we analyzed one proband with a severe FH phenotype as well as his relatives. Methods After the entire coding sequence and the intron-exon junctions of the low-density lipoprotein receptor （LDLR） gene were amplified using PCR, we sequenced the LDLR gene of a Chinese FH family. RT-PCR was used to detect changes in the mRNA. Results Two novel mutations were identified in the LDLR gene of this family. One, W165X, was a G〉A substitution at the third nucleotide of codon 165. The other, IVS5-1G〉A, was also a G〉A substitution at the acceptor splice site of intron 5. The most striking discovery is that the proband was heterozygous for W165X but homozygous for IVS5-1G〉A. The cDNA sequencing showed that the IVS5-1G〉A mutation caused the insertion of 10 nucleotides, namely GCTCTCACAA, between exon 5 and exon 6. Conclusions The two nucleotide variations are thought to be the FH-causing mutations because the co-segregation of the mutant allele with the phenotype of FH has been shown in this Chinese family. These data show an increase in the mutational spectrum of FH in China and verify a scarce mutational form in the LDLR gene.
基金a grant from the National Natural Science Foundation of China(No.30270734)
文摘Vascular endothelial growth factor （VEGF） is an angiogenic regulator that stimulates endothelial cell migration, proliferation, and angiogenesis. VEGF gene therapy is a new promising approach to induce therapeutic angiogenesis for the treatment of ischemic myocardial and limb diseases. Recently, clinical studies have demonstrated successful outcomes using plasmids, retroviruses and adenoviruses.l-3 But the safety of those vectors is poor, which has become a serious concern. Besides immunogenicity caused by viral vectors, a further problem is that viral vectors show a preference to integrate into the transcription or control region of active genes, which may induce tumors and other disorders.
