title: Mutation analysis of Wilson disease in the Spanish population -- identification of a prevalent substitution and eight novel mutations in the ATP7B gene.
abstract: Wilson disease (WD) is a copper metabolism disorder characterized by hepatic and/or neurological damage. More than 200 mutations in the ATP7B gene causing this autosomal recessive defect have been reported. In certain populations, a high prevalence of particular mutations allows rapid screening and diagnosis of the disease. We identified the ATP7B alterations in Spanish patients with WD. Mutations in the ATP7B gene were analysed in a total of 64 individuals from 40 different WD families by PCR amplification, single-strand conformation polymorphism (SSCP) analysis and sequencing. Twenty-one different ATP7B gene mutations were identified, eight of which were novel. 74% of the disease alleles were characterized among the 40 unrelated probands. We identified a prevalent mutation in our population (Met645Arg), present in 55% of this 40 patients. The frequency of the remaining ATP7B alterations was low. In addition, 17 different polymorphic variants were found. There is remarkable allele heterogeneity in WD in the Spanish population. Nevertheless, SSCP screening for the most frequent mutations in our population is feasible and leads to the detection of about 74% of the mutated chromosomes. Molecular diagnosis of WD is very useful in clinical practice to confirm or support clinical suspicion.
authors.affiliation: Department of Genetics, Hospital Clinic, Barcelona, Spain. margarit@clinic.ub.es
authors.forename: E
authors.initials: E
authors.lastname: Margarit
authors.forename: V
authors.initials: V
authors.lastname: Bach
authors.forename: D
authors.initials: D
authors.lastname: Gómez
authors.forename: M
authors.initials: M
authors.lastname: Bruguera
authors.forename: P
authors.initials: P
authors.lastname: Jara
authors.forename: R
authors.initials: R
authors.lastname: Queralt
authors.forename: F
authors.initials: F
authors.lastname: Ballesta
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000328:Adult; D019943:Amino Acid Substitution; D027682:Cation Transport Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D000073840:Copper-Transporting ATPases; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D005828:Genetics, Population; D006527:Hepatolenticular Degeneration / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic; D013030:Spain
chemical_list: D027682:Cation Transport Proteins; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases