H714Q mutation in Wilson disease is associated with late, neurological presentation

• Published in: Journal of medical genetics 1995-06, Vol.32 (6), p.480-482
• Main Authors: Houwen, R H, Juyn, J, Hoogenraad, T U, Ploos van Amstel, J K, Berger, R
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphatases - genetics; Adolescent; Adult; Age of Onset; Base Sequence; Biological and medical sciences; Cation Transport Proteins; Child; Copper - metabolism; Copper-transporting ATPases; DNA Mutational Analysis; Female; Hepatolenticular Degeneration - genetics; Homozygote; Humans; Male; Medical sciences; Metabolic diseases; Metals (hemochromatosis...); Molecular Sequence Data; Mutation; Other metabolic disorders; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.32.6.480

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.