OBJECTIVE: To investigate the characteristics of mutations in exon 3-20 of Wilson disease (WD) gene and their consequences in Chinese population. METHODS: Sixty unrelated normal Chinese and forty-four unrelated WD pat...OBJECTIVE: To investigate the characteristics of mutations in exon 3-20 of Wilson disease (WD) gene and their consequences in Chinese population. METHODS: Sixty unrelated normal Chinese and forty-four unrelated WD patients were studied. Genomic DNA was prepared from peripheral blood leukocytes by a salt-out method. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and subsequently direct sequencing were used to identify the mutations and polymorphisms of WD gene. RESULTS: Ten different mutations have been found, accounting for 52% of the mutant genes. Five of them are identified as novel missense mutations. Mutations Arg778Leu, Thr935Met and Ala874Val were represented respectively in 28.4%, 6.8% and 3.4% of WD chromosomes. The remaining mutations were found rare and limited to one or two patients. A total of 11 patients were homozygous for a single mutation, and 17 patients were in a compound heterozygous state with or without a known mutation. CONCLUSION: In Chinese, WD seems to result from two or three relatively common mutations and a large number of rare mutations. Arg778Leu and Thr935Met might be hotspots of mutation in Chinese population. The results indicated that the feature of mutations of WD gene is different between Chinese and the Western. Instead of exon 14 and exon 18, we had to select exon 8 and exon 12 first to detect mutations of WD gene in Chinese. It is of great importance to establish a direct diagnostic method for WD. This study improves our knowledge on functional domains of the WD gene, and helps elucidate the wide spectrum of manifestations of the disease as well.展开更多
近年来有研究发现,肿瘤细胞中普遍存在镁离子的稳态失衡,镁离子的缺失和补充可以影响肿瘤的发生和发展。镁离子作为细胞内丰富的二价阳离子,其在维持遗传稳定性、新陈代谢、细胞生长增殖和信号转导等生理过程发挥着重要作用。镁离子稳...近年来有研究发现,肿瘤细胞中普遍存在镁离子的稳态失衡,镁离子的缺失和补充可以影响肿瘤的发生和发展。镁离子作为细胞内丰富的二价阳离子,其在维持遗传稳定性、新陈代谢、细胞生长增殖和信号转导等生理过程发挥着重要作用。镁离子稳态受多种转运蛋白调控,有关镁离子转运蛋白的表达变化导致镁离子稳态失衡,进而影响肿瘤发生、发展及预后的研究报道已引起广泛关注。本文就镁离子及其相关转运蛋白[镁离子瞬时受体电位通道(transient receptor potential melastatin,TRPM)蛋白、镁离子转运(magnesium transporter,MagT)蛋白、细胞周期素和胱硫醚β-合成酶(cystathionineβ-synthase,CBS)结构域金属离子转运介质(cyclin and CBS domain divalent metal cation transport mediator,CNNM)蛋白和溶质载体(solute carrier,SLC)蛋白等]在肿瘤中的相关报道作一综述,旨在探索镁离子及其转运蛋白能否成为肿瘤诊断、治疗及预后的新靶点提供一条新的思路。展开更多
文摘OBJECTIVE: To investigate the characteristics of mutations in exon 3-20 of Wilson disease (WD) gene and their consequences in Chinese population. METHODS: Sixty unrelated normal Chinese and forty-four unrelated WD patients were studied. Genomic DNA was prepared from peripheral blood leukocytes by a salt-out method. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and subsequently direct sequencing were used to identify the mutations and polymorphisms of WD gene. RESULTS: Ten different mutations have been found, accounting for 52% of the mutant genes. Five of them are identified as novel missense mutations. Mutations Arg778Leu, Thr935Met and Ala874Val were represented respectively in 28.4%, 6.8% and 3.4% of WD chromosomes. The remaining mutations were found rare and limited to one or two patients. A total of 11 patients were homozygous for a single mutation, and 17 patients were in a compound heterozygous state with or without a known mutation. CONCLUSION: In Chinese, WD seems to result from two or three relatively common mutations and a large number of rare mutations. Arg778Leu and Thr935Met might be hotspots of mutation in Chinese population. The results indicated that the feature of mutations of WD gene is different between Chinese and the Western. Instead of exon 14 and exon 18, we had to select exon 8 and exon 12 first to detect mutations of WD gene in Chinese. It is of great importance to establish a direct diagnostic method for WD. This study improves our knowledge on functional domains of the WD gene, and helps elucidate the wide spectrum of manifestations of the disease as well.
文摘近年来有研究发现,肿瘤细胞中普遍存在镁离子的稳态失衡,镁离子的缺失和补充可以影响肿瘤的发生和发展。镁离子作为细胞内丰富的二价阳离子,其在维持遗传稳定性、新陈代谢、细胞生长增殖和信号转导等生理过程发挥着重要作用。镁离子稳态受多种转运蛋白调控,有关镁离子转运蛋白的表达变化导致镁离子稳态失衡,进而影响肿瘤发生、发展及预后的研究报道已引起广泛关注。本文就镁离子及其相关转运蛋白[镁离子瞬时受体电位通道(transient receptor potential melastatin,TRPM)蛋白、镁离子转运(magnesium transporter,MagT)蛋白、细胞周期素和胱硫醚β-合成酶(cystathionineβ-synthase,CBS)结构域金属离子转运介质(cyclin and CBS domain divalent metal cation transport mediator,CNNM)蛋白和溶质载体(solute carrier,SLC)蛋白等]在肿瘤中的相关报道作一综述,旨在探索镁离子及其转运蛋白能否成为肿瘤诊断、治疗及预后的新靶点提供一条新的思路。
