title: Disturbed copper transport in humans. Part 2: mutations of the ATP7B gene lead to Wilson disease (WD).
abstract: Mutations in the Wilson disease gene ATP7B, a P-type ATPase, are responsible for copper accumulation in the liver and other organs leading to Wilson disease (WD, OMIM 277900). Clinical manifestations of Wilson disease (WD) include chronic liver disease, acute hepatic failure or neuropsychiatric diseases. Since potent medical treatments are available to prevent disabling residual symptoms, early diagnosis is crucial. To demonstrate the clinical course and genetic findings, a male patient with a novel mutation in the ATP7B gene, a 10 base pair insertion in exon 6 (1927ins 10), and a second missense mutation in exon 13 (P992L) is reported. The patient presented with signs of chronic liver disease at the age of 10 years. Clinical findings included hepatomegaly, elevated liver enzymes and coagulopathy. A combination treatment with the copper chelating agent D-penicillamine and zinc acetate was started leading to normalization of liver function and no appearance of neurological signs or Kayser-Fleischer ring after 7 years follow-up. Truncating mutations of the ATP7B gene (insertions, deletions, nonsense mutations) leading to gross loss of C-terminal parts of the protein, thereby probably completely destroying the protein function, may correlate with a hepatic phenotype and early onset as seen in the patient presented.
authors.affiliation: Department of Pediatrics, Friedrich-Schiller University Jena, Germany. joerg.seidel@med.uni-jena.de
authors.forename: J
authors.initials: J
authors.lastname: Seidel
authors.forename: K
authors.initials: K
authors.lastname: Caca
authors.forename: S G
authors.initials: SG
authors.lastname: Schwab
authors.forename: F
authors.initials: F
authors.lastname: Berr
authors.forename: D B
authors.initials: DB
authors.lastname: Wildenauer
authors.forename: H J
authors.initials: HJ
authors.lastname: Mentzel
authors.forename: N
authors.initials: N
authors.lastname: Horn
authors.forename: E
authors.initials: E
authors.lastname: Kauf
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000293:Adolescent; D001483:Base Sequence; D027682:Cation Transport Proteins / Q000235:genetics*; D003300:Copper / Q000378:metabolism* / Q000652:urine; D000073840:Copper-Transporting ATPases; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons; D005838:Genotype; D006527:Hepatolenticular Degeneration / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D010396:Penicillamine / Q000627:therapeutic use; D010641:Phenotype; D019345:Zinc Acetate / Q000627:therapeutic use
chemical_list: D027682:Cation Transport Proteins; D003300:Copper; D004247:DNA; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases; D019345:Zinc Acetate; D010396:Penicillamine