title: Novel mutations of the ATP7B gene in Han Chinese families with pre-symptomatic Wilson's disease.
abstract: BACKGROUND
  Wilson's disease (WD) is an autosomal recessive genetic disorder of copper metabolism, caused by mutations in the ATP7B gene, resulting in copper accumulation in the liver, brain, kidney, and cornea and leading to significant disability or death if untreated. Early diagnosis and proper therapy usually predict a good prognosis, especially in pre-symptomatic WD. Genetic testing is the most accurate and effective diagnostic method for early diagnosis.
  
  
  METHODS
  The clinical and biochemical features of three unrelated Han Chinese families with pre-symptomatic WD were reported. The molecular defects in these families were investigated by polymerase chain reaction and DNA sequencing. Hundred healthy children with the same ethnic background served as controls. Bioinformatic tools (polymorphism phenotyping-2, sorting intolerant from tolerant, protein analysis through evolutionary relationships, and predictor of human deleterious single nucleotide polymorphisms) were combined and used to predict the functional effects of mutations.
  
  
  RESULTS
  We identified 2 novel ATP7B mutations (p.Leu692Pro and p.Asn728Ser) and 3 known mutations (p.Met769fs, p.Arg778Leu and p.Val1216Met) in these Chinese WD families. These mutations were not observed in the 100 normal controls. The bioinformatic method showed that p.Leu692Pro and p.Asn728Ser mutations are pathogenic.
  
  
  CONCLUSIONS
  Our research enriches the mutation spectrum of the ATP7B gene worldwide and provides valuable information for studying the mutation types and mode of inheritance of ATP7B in the Chinese population. Liver function analysis and genetic testing in young children with WD are necessary to shorten the time to the initiation of therapy, reduce damage to the liver and brain, and improve prognosis.
authors.affiliation: Department of Neurology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
authors.forename: Zhe-Feng
authors.initials: ZF
authors.lastname: Yuan
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Yong-Lin
authors.initials: YL
authors.lastname: Yu
authors.forename: Jue
authors.initials: J
authors.lastname: Shen
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Mao
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Zhe-Zhi
authors.initials: ZZ
authors.lastname: Xia
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D027682:Cation Transport Proteins / Q000235:genetics*; D002675:Child, Preschool; D002681:China; D015331:Cohort Studies; D003300:Copper / Q000627:therapeutic use; D000073840:Copper-Transporting ATPases; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D006527:Hepatolenticular Degeneration / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D018570:Risk Assessment; D016896:Treatment Outcome
chemical_list: D027682:Cation Transport Proteins; D003300:Copper; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases