title: Clinical and molecular characterization of Wilson's disease in China: identification of 14 novel mutations.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.forename: Yun
authors.initials: Y
authors.lastname: Ling
authors.forename: Qing-Chun
authors.initials: QC
authors.lastname: Fu
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Zang
authors.forename: Feng
authors.initials: F
authors.lastname: Zhou
authors.forename: Yu
authors.initials: Y
authors.lastname: De-Min
authors.forename: Yue
authors.initials: Y
authors.lastname: Han
authors.forename: Dong-Hua
authors.initials: DH
authors.lastname: Zhang
authors.forename: Qi-Ming
authors.initials: QM
authors.lastname: Gong
authors.forename: Zhi-Meng
authors.initials: ZM
authors.lastname: Lu
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Kong
authors.forename: Jian-She
authors.initials: JS
authors.lastname: Wang
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Zhang
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000032:analysis; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D027682:Cation Transport Proteins / Q000235:genetics*; D002570:Ceruloplasmin / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D003300:Copper / Q000652:urine; D000073840:Copper-Transporting ATPases; D005091:Exons; D005260:Female; D005820:Genetic Testing; D006527:Hepatolenticular Degeneration / Q000175:diagnosis / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D055815:Young Adult
chemical_list: D027682:Cation Transport Proteins; D003300:Copper; D002570:Ceruloplasmin; D000410:Alanine Transaminase; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases