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mutations, disease, patients, article, pubmed, google, scholar, wnd, diagnosis, mutation, cas, atpb, wilson, figure, copper, clinical, chinese, gene, manifestations, china, liver, wilsons, pargleu, age, levels, correlation, neurologic, analysis, journal, hepatic, shanghai, genetics, urinary, data, identified, ceruloplasmin, file, authors, function, probands, population, years, serum, genetic, symptoms, human, supplementary, table, zhang, children,

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xiao-fei kong & xin-xin zhang sino-french research center copper-transporting p-type atpase xin-hua li xin-xin zhang open access article xiao-fei kong pre-publication history coombs-negative hemolytic anemia pubmed search supplementary table s4 combined search terms supplementary table s3 sm/sm group presented qing-chun fu article download pdf supplementary table s2 cornea kayser-fleischer ring corneal kayser-fleischer ring kruskal-wallis anova test human copper-transporting atpases shapiro-wilk normality test supplementary table s5 early clinical manifestation evaluating genotype-phenotype correlations full size image predicting amino acid dong-hua zhang copper transporting atpase supplementary table s1 article li corneal kayser-fleischer rings atp-binding domain typical splice-site mutations tend large-scale wnd screening abnormal copper metabolism related subjects low serum ceruloplasmin biophysical research communications nucleic acids research lower serum ceruloplasmin serum ceruloplasmin levels potential genotype-phenotype correlation low plasma ceruloplasmin motor coordination longer diagnostic delay privacy choices/manage cookies guo-qing zang serum ceruloplasmin concentration hong kong chinese

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         headline:Clinical and molecular characterization of Wilson's disease in China: identification of 14 novel mutations
         description:Wilson's disease (WND) is a rare autosomal recessive disorder. Here we have evaluated 62 WND cases (58 probands) from the Chinese Han population to expand our knowledge of ATP7B mutations and to more completely characterize WND in China. The coding and promoter regions of the ATP7B gene were analyzed by direct sequencing in 62 Chinese patients (58 probands) with WND (male, n = 37; female, n = 25; age range, 2 ~ 61 years old). Neurologic manifestations were associated with older age at diagnosis (p < 0.0001) and longer diagnostic delay (p < 0.0001). Age at diagnosis was also correlated with urinary copper concentration (r = 0.58, p < 0.001). Forty different mutations, including 14 novel mutations, were identified in these patients. Common mutations included p.Arg778Leu (31.9%) and p.Pro992Leu (11.2%). Homozygous p.Arg778Leu and nonsense mutation/frameshift mutations were more often associated with primary hepatic manifestations (p = 0.0286 and p = 0.0383, respectively) and higher alanine transaminase levels at diagnosis (p = 0.0361 and p = 0.0047, respectively). Nonsense mutation/frameshift mutations were also associated with lower serum ceruloplasmin (p = 0.0065). We identified 14 novel mutations and found that the spectrum of mutations of ATP7B in China is quite distinct from that of Western countries. The mutation type plays a role in predicting clinical manifestations. Genetic testing is a valuable tool to detect WND in young children, especially in patients younger than 8 years old. Four exons (8, 12, 13, and 16) and two mutations (p.Arg778Leu, p.Pro992Leu) should be considered high priority for cost-effective testing in China.
         datePublished:2011-01-11T00:00:00Z
         dateModified:2011-01-11T00:00:00Z
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            Neurologic Manifestation
            Wilson Disease
            Diagnostic Delay
            Serum Ceruloplasmin
            ATP7B Gene
            Human Genetics
            Cytogenetics
            Gene Function
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      headline:Clinical and molecular characterization of Wilson's disease in China: identification of 14 novel mutations
      description:Wilson's disease (WND) is a rare autosomal recessive disorder. Here we have evaluated 62 WND cases (58 probands) from the Chinese Han population to expand our knowledge of ATP7B mutations and to more completely characterize WND in China. The coding and promoter regions of the ATP7B gene were analyzed by direct sequencing in 62 Chinese patients (58 probands) with WND (male, n = 37; female, n = 25; age range, 2 ~ 61 years old). Neurologic manifestations were associated with older age at diagnosis (p < 0.0001) and longer diagnostic delay (p < 0.0001). Age at diagnosis was also correlated with urinary copper concentration (r = 0.58, p < 0.001). Forty different mutations, including 14 novel mutations, were identified in these patients. Common mutations included p.Arg778Leu (31.9%) and p.Pro992Leu (11.2%). Homozygous p.Arg778Leu and nonsense mutation/frameshift mutations were more often associated with primary hepatic manifestations (p = 0.0286 and p = 0.0383, respectively) and higher alanine transaminase levels at diagnosis (p = 0.0361 and p = 0.0047, respectively). Nonsense mutation/frameshift mutations were also associated with lower serum ceruloplasmin (p = 0.0065). We identified 14 novel mutations and found that the spectrum of mutations of ATP7B in China is quite distinct from that of Western countries. The mutation type plays a role in predicting clinical manifestations. Genetic testing is a valuable tool to detect WND in young children, especially in patients younger than 8 years old. Four exons (8, 12, 13, and 16) and two mutations (p.Arg778Leu, p.Pro992Leu) should be considered high priority for cost-effective testing in China.
      datePublished:2011-01-11T00:00:00Z
      dateModified:2011-01-11T00:00:00Z
      pageStart:1
      pageEnd:13
      license:https://creativecommons.org/licenses/by/2.0
      sameAs:https://doi.org/10.1186/1471-2350-12-6
      keywords:
         Neurologic Manifestation
         Wilson Disease
         Diagnostic Delay
         Serum Ceruloplasmin
         ATP7B Gene
         Human Genetics
         Cytogenetics
         Gene Function
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