Analysis of the T1288R Mutation of the Wilson Disease ATP7B Gene in Four Generations of a Family: Possible Genotype-Phenotype Correlation with Hepatic Onset

摘要

Wilson disease, an autosomal recessive disorder due to mutations of the ATP7B gene, is characterized by copper accumulation and toxicity in the liver and subsequently in other organs, mainly the brain and cornea. A new missense mutation (T1288R) of the ATP7B gene has recently been discovered in a Wilson disease patient in our laboratory. The aim of the present study was to analyze clinical and genetic features of more generations of the family of the patient in which the new mutation T1288R was discovered. A total of 19 subjects were studied; in particular, four generations of the patient’s family were analyzed. The ATP7B gene was analyzed by single-strand conformational polymorphism followed by direct sequencing. Two brothers presented a clinical diagnosis of Wilson disease with an hepatic phenotype and a genotype characterized by the homozygotic mutation T1288R. The heterozygotic mutation T1288R was found in seven subjects belonging to all four generations. The present study represents the first screening for a Wilson disease mutation through four generations of a nonconsanguineous family. All the patients with the homozygotic T1288R mutation in the present pedigree presented an hepatic phenotype without a neurological presentation. Consequently, a genotype-phenotype correlation could be hypothesized, although further studies are necessary to clarify this topic.