title: Homozygosity for a gross partial gene deletion of the C-terminal end of ATP7B in a Wilson patient with hepatic and no neurological manifestations.
abstract: We identified a partial gene deletion of ATP7B in a patient with Wilson disease with hepatic onset. The deletion covered exon 20 including major parts of the flanking introns. The breakpoints were identified and the size of the deletion determined to be 2144 bp. The deletion is predicted to lead to a mutated protein product containing 45 aberrant amino acids after transmembrane domain 7, and lacking the transmembrane domain 8 as well as the entire C-terminal cytoplasmic tail. This is the first time a partial gene deletion has been demonstrated in ATP7B. The patient presented at age 10 with hepatic manifestations, including severe jaundice, hepato-splenomegaly, ascites, and spider naevi. The liver biopsy showed fibrosis and early signs of cirrhosis. There was a Kayser-Fleischer ring but no neurological manifestations. All symptoms disappeared with penicillamine therapy. This suggests that the C-terminal cytoplasmatic tail of ATP7B, is not essential for its neurological function. Large deletions in ATP7B may be an overlooked cause of Wilson disease. Patients that are homozygotes for deletions may be valuable for the understanding of the function of various regions of the ATP7B protein.
authors.affiliation: The Kennedy Institute, Gl. Landevej 7, DK 2600 Glostrup, Denmark.
authors.forename: Lisbeth Birk
authors.initials: LB
authors.lastname: Møller
authors.forename: Peter
authors.initials: P
authors.lastname: Ott
authors.forename: Connie
authors.initials: C
authors.lastname: Lund
authors.forename: Nina
authors.initials: N
authors.lastname: Horn
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D001483:Base Sequence; D027682:Cation Transport Proteins / Q000235:genetics*; D002648:Child; D000073840:Copper-Transporting ATPases; D017931:DNA Primers; D017353:Gene Deletion; D006720:Homozygote; D006801:Humans; D008107:Liver Diseases / Q000235:genetics*; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D027682:Cation Transport Proteins; D017931:DNA Primers; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases