AIM： To investigate the prevalence of the ATP7B gene mutation in patients with hepatic presentation of Wilson＇s disease （WD） in Lithuania. METHODS： Eleven unrelated Lithuanian families, including 13 WD patients w...AIM： To investigate the prevalence of the ATP7B gene mutation in patients with hepatic presentation of Wilson＇s disease （WD） in Lithuania. METHODS： Eleven unrelated Lithuanian families, including 13 WD patients were tested. Clinically WD diagnosis was established in accordance to the Leipzig scoring system. Genomic DNA was extracted from whole venous blood using a salt precipitation method. Firstly, the semi-nested polymerase chain reaction （PCR） technique was used to detect the c.3207C〉A （p.H1069Q） mutation. Patients not homozygous for the c.3207C〉A （p.H1069Q） mutation were further analyzed. The 21 exons of the WD gene were amplified in a thermal cycler （Biometra T3 Thermocycler, G0ttingen, Germany）. Direct sequencing of the amplified PCR products was performed by cycle sequencing using fluorescent dye terminators in an automatic sequencer （Applied Biosystems, Darmstadt, Germany）. RESULTS： Total of 13 WD patients （mean age 26.4 years; range 17-40; male/female 3/10） presented with hepatic disorders and 16 their first degree relatives （including 12 siblings） were studied. Some of WD patients, in addition to hepatic symptoms, have had extrahepatic disorders （hemolytic anemia 3; Fanconi syndrome 1; neurophsychiatric and behavioural disorder 2）. Liver biopsy specimens were available in all of 13 WD patients （8 had cirrhosis; 1-chronic hepatitis; 3-acute liver failure, 1-1iver steatosis）. Twelve of 13 （92.3%） WD patients had the c.3207C〉A （p.HI069Q） mutation, 6 of them in both chromosomes, 6 were presented as compound heterozygotes with additional c.3472-82delGGTTTAACCAT, c.3402delC, c.3121C〉T （p.RI041W） or unknown mutations. For one patient with liver cirrhosis and psychiatric disorder （Leipzig score 6）, no mutations were found. Out of 16 first degree WD relatives, 11 （68.7%） were heterozygous for the c.3207C〉A （p.H1069Q） mutation. Two patients with fulminant WD died from acute liver failure and ii are in full remission under peniciilamine or zinc acetate treatment. Three women with WD successfully delivered healthy babies. CONCLUSION： The c.3207C〉A （p.HI069Q） missense mutation is the most characteristic mutation for Lithuanian patients with WD. Even 92.3% of WD patients with hepatic presentation of the disease are homozygous or compound heterozygotes for the p.H1069Q mutation.展开更多
Wilson disease is an hereditary disorder of copper metabolism, caused by mutations in the ATP7B gene, and leading to hepatic or neurologic disease. We examined whether H1069Q, the most common ATP7B mutation, is associ...Wilson disease is an hereditary disorder of copper metabolism, caused by mutations in the ATP7B gene, and leading to hepatic or neurologic disease. We examined whether H1069Q, the most common ATP7B mutation, is associated with a specific phenotype. Genotyping results in 70 Dutch patients were related to clinical presentation. Subsequently a meta-analysis for genotype-phenotype correlation was performed on all patients available from literature, combined with the current Dutch group, a total of 577 patients. The Dutch patients homozygous or heterozygous for the H1069Q mutation presented more frequently with neurologic disease (63%and 43%vs. 15%), and at a later age (20.9 and 15.9 vs. 12.6 years) than patients without the H1069Q mutation. In the meta-analysis the odds-ratio for neurologic presentation in homozygous or heterozygous H1069Q vs. non-H1069Q patients was 3.50 (95%CI 2.01-6.09) and 2.13 (95%CI 1.18-3.83), respectively. Age at presentation was 21.1, 19.2 and 16.5 years, respectively, corresponding to a weighted mean difference (WMD) of 4.41 (95%CI 1.56-7.26) for homozygous H1069Q vs. heterozygous patients and 6.68 (95%CI 4.33-9.38) for homozygous H1069Q vs. non-H1069Q patients. Our results indicate that the H1069Q mutation is associated with a late and neurologic presentation.展开更多
Objective:Lilium brownii var.viridulum(LB)and L.lancifolium(LL)are the main sources of medicinal lily(Lilii Bulbus,Baihe in Chinese)in China.However,the functional components of these two species responsible for the t...Objective:Lilium brownii var.viridulum(LB)and L.lancifolium(LL)are the main sources of medicinal lily(Lilii Bulbus,Baihe in Chinese)in China.However,the functional components of these two species responsible for the treatment efficacy are yet not clear.In order to explore the therapeutic material basis of Lilii Bulbus,we selected L.davidii var.willmottiae(LD)only used for food as the control group to analyze the differences between LD and the other two(LB and LL).Methods:Metabolome and transcriptome were carried out to investigate the differences of active components in LD vs LB and LD vs LL.Data of metabolome and transcriptome was analysed using various analysis methods,such as principal component analysis(PCA),hierarchical cluster analysis(HCA),and so on.Differentially expressed genes(DEGs)were enriched through KEGG and GO enrichment analysis.Results:The PCA and HCA of the metabolome indicated the metabolites were clearly separated and varied greatly in LL and LB contrasted with LD.There were 318 significantly differential metabolites(SDMs)in LD vs LB group and 298 SDMs in LD vs LL group.Compared with LD group,the significant up-regulation of steroidal saponins and steroidal alkaloids were detected both in LB and LL groups,especially in LB group.The HCA of transcriptome indicated that there was significant difference in LB vs LD group,while the difference between LL and LD varied slightly.Additionally,47540 DEGs in LD vs LB group and 18958 DEGs in LD vs LL group were identified.Notably,CYP450s involving in the biosynthesis of steroidal saponins and steroidal alkaloids were detected,and comparing with LD,CYP724,CYP710A,and CYP734A1 in LB and CYP90B in LL were all up-regulated.Conclusion:This study suggested that steroidal saponins and steroidal alkaloids maybe the representative functional components of Lilii Bulbus,which can provide new insights for Lilii Bulbus used in the research and development of classic famous formula.展开更多
基金The National Science and Education Foundation of Lithuania, No. M-06005
文摘AIM： To investigate the prevalence of the ATP7B gene mutation in patients with hepatic presentation of Wilson＇s disease （WD） in Lithuania. METHODS： Eleven unrelated Lithuanian families, including 13 WD patients were tested. Clinically WD diagnosis was established in accordance to the Leipzig scoring system. Genomic DNA was extracted from whole venous blood using a salt precipitation method. Firstly, the semi-nested polymerase chain reaction （PCR） technique was used to detect the c.3207C〉A （p.H1069Q） mutation. Patients not homozygous for the c.3207C〉A （p.H1069Q） mutation were further analyzed. The 21 exons of the WD gene were amplified in a thermal cycler （Biometra T3 Thermocycler, G0ttingen, Germany）. Direct sequencing of the amplified PCR products was performed by cycle sequencing using fluorescent dye terminators in an automatic sequencer （Applied Biosystems, Darmstadt, Germany）. RESULTS： Total of 13 WD patients （mean age 26.4 years; range 17-40; male/female 3/10） presented with hepatic disorders and 16 their first degree relatives （including 12 siblings） were studied. Some of WD patients, in addition to hepatic symptoms, have had extrahepatic disorders （hemolytic anemia 3; Fanconi syndrome 1; neurophsychiatric and behavioural disorder 2）. Liver biopsy specimens were available in all of 13 WD patients （8 had cirrhosis; 1-chronic hepatitis; 3-acute liver failure, 1-1iver steatosis）. Twelve of 13 （92.3%） WD patients had the c.3207C〉A （p.HI069Q） mutation, 6 of them in both chromosomes, 6 were presented as compound heterozygotes with additional c.3472-82delGGTTTAACCAT, c.3402delC, c.3121C〉T （p.RI041W） or unknown mutations. For one patient with liver cirrhosis and psychiatric disorder （Leipzig score 6）, no mutations were found. Out of 16 first degree WD relatives, 11 （68.7%） were heterozygous for the c.3207C〉A （p.H1069Q） mutation. Two patients with fulminant WD died from acute liver failure and ii are in full remission under peniciilamine or zinc acetate treatment. Three women with WD successfully delivered healthy babies. CONCLUSION： The c.3207C〉A （p.HI069Q） missense mutation is the most characteristic mutation for Lithuanian patients with WD. Even 92.3% of WD patients with hepatic presentation of the disease are homozygous or compound heterozygotes for the p.H1069Q mutation.
文摘Wilson disease is an hereditary disorder of copper metabolism, caused by mutations in the ATP7B gene, and leading to hepatic or neurologic disease. We examined whether H1069Q, the most common ATP7B mutation, is associated with a specific phenotype. Genotyping results in 70 Dutch patients were related to clinical presentation. Subsequently a meta-analysis for genotype-phenotype correlation was performed on all patients available from literature, combined with the current Dutch group, a total of 577 patients. The Dutch patients homozygous or heterozygous for the H1069Q mutation presented more frequently with neurologic disease (63%and 43%vs. 15%), and at a later age (20.9 and 15.9 vs. 12.6 years) than patients without the H1069Q mutation. In the meta-analysis the odds-ratio for neurologic presentation in homozygous or heterozygous H1069Q vs. non-H1069Q patients was 3.50 (95%CI 2.01-6.09) and 2.13 (95%CI 1.18-3.83), respectively. Age at presentation was 21.1, 19.2 and 16.5 years, respectively, corresponding to a weighted mean difference (WMD) of 4.41 (95%CI 1.56-7.26) for homozygous H1069Q vs. heterozygous patients and 6.68 (95%CI 4.33-9.38) for homozygous H1069Q vs. non-H1069Q patients. Our results indicate that the H1069Q mutation is associated with a late and neurologic presentation.
基金funded by 2022 Provincial Science and Technology Research and Development Plan United Fund(No.222301420075)Henan Provincial High-Level Talents International Training Funding Project(No.2021-72).
文摘Objective:Lilium brownii var.viridulum(LB)and L.lancifolium(LL)are the main sources of medicinal lily(Lilii Bulbus,Baihe in Chinese)in China.However,the functional components of these two species responsible for the treatment efficacy are yet not clear.In order to explore the therapeutic material basis of Lilii Bulbus,we selected L.davidii var.willmottiae(LD)only used for food as the control group to analyze the differences between LD and the other two(LB and LL).Methods:Metabolome and transcriptome were carried out to investigate the differences of active components in LD vs LB and LD vs LL.Data of metabolome and transcriptome was analysed using various analysis methods,such as principal component analysis(PCA),hierarchical cluster analysis(HCA),and so on.Differentially expressed genes(DEGs)were enriched through KEGG and GO enrichment analysis.Results:The PCA and HCA of the metabolome indicated the metabolites were clearly separated and varied greatly in LL and LB contrasted with LD.There were 318 significantly differential metabolites(SDMs)in LD vs LB group and 298 SDMs in LD vs LL group.Compared with LD group,the significant up-regulation of steroidal saponins and steroidal alkaloids were detected both in LB and LL groups,especially in LB group.The HCA of transcriptome indicated that there was significant difference in LB vs LD group,while the difference between LL and LD varied slightly.Additionally,47540 DEGs in LD vs LB group and 18958 DEGs in LD vs LL group were identified.Notably,CYP450s involving in the biosynthesis of steroidal saponins and steroidal alkaloids were detected,and comparing with LD,CYP724,CYP710A,and CYP734A1 in LB and CYP90B in LL were all up-regulated.Conclusion:This study suggested that steroidal saponins and steroidal alkaloids maybe the representative functional components of Lilii Bulbus,which can provide new insights for Lilii Bulbus used in the research and development of classic famous formula.
