title: H714Q mutation in Wilson disease is associated with late, neurological presentation.
abstract: Wilson disease is an autosomal recessive copper storage disease resulting from an inability of the liver to excrete copper. Patients can present at a young age, generally with symptoms of liver copper intoxication, or later on, generally with neurological symptoms. The gene for Wilson disease has recently been cloned. Five mutations have been described so far, but only one is found frequently, H714Q. We analysed 38 Dutch symptomatic Wilson disease patients for the H714Q mutation and correlated this finding with age and symptoms at presentation. Ten patients homozygous for the H714Q mutation presented at a mean age of 20.3 (SD 6.1) years, with either neurological symptoms or a Kayser-Fleischer ring. Six patients with a H714Q mutation in one chromosome and an unknown mutation in the other chromosome presented at a mean age of 17.8 (SD 5.8) years, with either neurological or hepatic symptoms. With the exception of one, all 22 patients with an uncharacterised mutation in both chromosomes presented with liver involvement, at a mean age of 9.9 (SD 2.4) years. The difference in age at presentation between the H714Q/H714Q group and the patients with an unknown mutation was highly significant (p < 0.0001). This suggests that the H714Q mutation represents a relatively mild mutation, possibly with some residual function in the copper transporting protein, resulting in a slower build up of copper.
authors.affiliation: Department of Paediatric Gastroenterology, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
authors.forename: R H
authors.initials: RH
authors.lastname: Houwen
authors.forename: J
authors.initials: J
authors.lastname: Juyn
authors.forename: T U
authors.initials: TU
authors.lastname: Hoogenraad
authors.forename: J K
authors.initials: JK
authors.lastname: Ploos van Amstel
authors.forename: R
authors.initials: R
authors.lastname: Berger
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001483:Base Sequence; D027682:Cation Transport Proteins; D002648:Child; D003300:Copper / Q000378:metabolism; D000073840:Copper-Transporting ATPases; D004252:DNA Mutational Analysis; D005260:Female; D006527:Hepatolenticular Degeneration / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D027682:Cation Transport Proteins; D003300:Copper; D000251:Adenosine Triphosphatases; D000073840:Copper-Transporting ATPases