Objective： Tile objective of this study was to review the research on clinical genetics of Wilson＇s disease （WD）. Data Sources： We searched docunlents from PubMed and Wanfang databases both in English and Chinese...Objective： Tile objective of this study was to review the research on clinical genetics of Wilson＇s disease （WD）. Data Sources： We searched docunlents from PubMed and Wanfang databases both in English and Chinese up to 2014 using the keywords WD in combination with genetic,ATP7B gene, gene mntation, genotype, phenotype. Study Selection： Publications about the ATP7B gene and protein timction associated with clinical features were selected. Results： Wilson＇s disease, also named hepatolenticular degeneration, is an autosomal recessive genetic disorder characterized by abnormal copper metabolism caused by mutations to the copper-transporting gene A TP7B. Decreased biliary copper excretion and redtlced incorporation of copper into apoeeruloplasmin caused by defunctionalization of ATP7B protein lead to acct, mulation of copper in many tissues and organs, including liver; brain, and cornea, finally restllting in liver disease and extrapyramidal symptoms. It is the most common genetic neurological disorder in the onset of adolescents, second to muscular dystrophy in China. Early diagnosis and medical therapy are of great significance tbr improving the prognosis of WD patients. However, diagnosis of this disease is usually diffict.lt because of its complicated phenotypes. In the last l0 years, an increasing number of clinical studies have used molecular genetics techniques. Improved diagnosis and prediction ol＇the progression of this disease at the molecular level will aid in the development of more individualized and effective intervcntions, which is a key to transition from molecular genetic research to the clinical study. Conclusions： Clinical genetics studies are necessary to understand the mechanism underlying WD at the molecular level from the genotype to the phenotype. Clinical genetics research benefits newly emerging medical treatments including stem cell transplantation and gone therapy for WD patients.展开更多
AIM： To investigate the impact of dietary copper given at different time points on the onset of fulminant hepatitis. METHODS： The Long-Evans cinnamon （LEC） rat mod- el of Wilson＇s disease （WD） was used to study...AIM： To investigate the impact of dietary copper given at different time points on the onset of fulminant hepatitis. METHODS： The Long-Evans cinnamon （LEC） rat mod- el of Wilson＇s disease （WD） was used to study the im- pact of high dietary copper （hCu） on the induction of fulminant hepatitis at early or late time points of life. High Cu diet was started in rat pups or in adults （month 5） for three months. Animals that received reduced di- etary copper （rCu） throughout their lifetime served as a control. Hepatitis-associated serum markers （alanine aminotransferase, aspartate transaminase, bilirubin） were analyzed in animal groups receiving hCu or rCu. Liver copper content and liver histology were revealed at sacrifice. A set of 5 marker genes previously found to be affected in injured liver and which are related to angiogenesis （Vegfa）, fat metabolism （Srebf1）, ex- tracellular matrix （Timp1）, oxidative stress （Hmox1）, and the cell cycle （Cdknla） were analyzed by real-time polymerase chain reaction. RESULTS： Regardless of the time point when hCu was started, LEC rats （35/36） developed fulminant hepati- tis and died. Animals receiving rCu （36/36） remained healthy, did not develop hepatitis, and survived long term without symptoms of overt disease, although liver copper accumulated in adult animals （477 ± 75 μg/g）. With regard to start of hCu, onset of fulminant hepatitis was significantly （P 〈 0.001） earlier in adults （35±9 d） that showed pre-accumulation of liver copper as com- pared to the pup group （77±15 d）. Hepatitis-associ- ated serum markers, liver copper and liver histology, as well as gene expression, were affected in LEC rats re- ceiving hCu. However, except for early and rapid onset of hepatitis, biochemical and molecular markers were similar at the early and late time points of disease. CONCLUSION： Rapid onset of fulminant hepatitis in asymptomatic LEC rats with elevated liver copper sug- gests that there is a critical th展开更多
基金This research was supported by National Natural Science Foundation of China
文摘Objective： Tile objective of this study was to review the research on clinical genetics of Wilson＇s disease （WD）. Data Sources： We searched docunlents from PubMed and Wanfang databases both in English and Chinese up to 2014 using the keywords WD in combination with genetic,ATP7B gene, gene mntation, genotype, phenotype. Study Selection： Publications about the ATP7B gene and protein timction associated with clinical features were selected. Results： Wilson＇s disease, also named hepatolenticular degeneration, is an autosomal recessive genetic disorder characterized by abnormal copper metabolism caused by mutations to the copper-transporting gene A TP7B. Decreased biliary copper excretion and redtlced incorporation of copper into apoeeruloplasmin caused by defunctionalization of ATP7B protein lead to acct, mulation of copper in many tissues and organs, including liver; brain, and cornea, finally restllting in liver disease and extrapyramidal symptoms. It is the most common genetic neurological disorder in the onset of adolescents, second to muscular dystrophy in China. Early diagnosis and medical therapy are of great significance tbr improving the prognosis of WD patients. However, diagnosis of this disease is usually diffict.lt because of its complicated phenotypes. In the last l0 years, an increasing number of clinical studies have used molecular genetics techniques. Improved diagnosis and prediction ol＇the progression of this disease at the molecular level will aid in the development of more individualized and effective intervcntions, which is a key to transition from molecular genetic research to the clinical study. Conclusions： Clinical genetics studies are necessary to understand the mechanism underlying WD at the molecular level from the genotype to the phenotype. Clinical genetics research benefits newly emerging medical treatments including stem cell transplantation and gone therapy for WD patients.
基金Supported by Deutsche Forschungsgemeinschaft, SCHM 964/10-1Innovative Medizinische Forschung, Münster
文摘AIM： To investigate the impact of dietary copper given at different time points on the onset of fulminant hepatitis. METHODS： The Long-Evans cinnamon （LEC） rat mod- el of Wilson＇s disease （WD） was used to study the im- pact of high dietary copper （hCu） on the induction of fulminant hepatitis at early or late time points of life. High Cu diet was started in rat pups or in adults （month 5） for three months. Animals that received reduced di- etary copper （rCu） throughout their lifetime served as a control. Hepatitis-associated serum markers （alanine aminotransferase, aspartate transaminase, bilirubin） were analyzed in animal groups receiving hCu or rCu. Liver copper content and liver histology were revealed at sacrifice. A set of 5 marker genes previously found to be affected in injured liver and which are related to angiogenesis （Vegfa）, fat metabolism （Srebf1）, ex- tracellular matrix （Timp1）, oxidative stress （Hmox1）, and the cell cycle （Cdknla） were analyzed by real-time polymerase chain reaction. RESULTS： Regardless of the time point when hCu was started, LEC rats （35/36） developed fulminant hepati- tis and died. Animals receiving rCu （36/36） remained healthy, did not develop hepatitis, and survived long term without symptoms of overt disease, although liver copper accumulated in adult animals （477 ± 75 μg/g）. With regard to start of hCu, onset of fulminant hepatitis was significantly （P 〈 0.001） earlier in adults （35±9 d） that showed pre-accumulation of liver copper as com- pared to the pup group （77±15 d）. Hepatitis-associ- ated serum markers, liver copper and liver histology, as well as gene expression, were affected in LEC rats re- ceiving hCu. However, except for early and rapid onset of hepatitis, biochemical and molecular markers were similar at the early and late time points of disease. CONCLUSION： Rapid onset of fulminant hepatitis in asymptomatic LEC rats with elevated liver copper sug- gests that there is a critical th
