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

Abstract

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.

Application of Biotechnology in Detection ATP7B Gene Mutation in Vietnamese Children with Wilson Disease and Screening Target Mutation for Their Family Members

“…Tỷ lệ kiểu gen của bệnh nhân Wilson trong nghiên cứu tương tự với các thống kê trên thế giới. Theo đó, trong số 90% đột biến phát hiện trên gen ATP7B có 60% ở thể đột biến đồng hợp tử hoặc dị hợp tử kép, 30% chỉ có một đột biến dị hợp tử [6,27]. Xác định kiểu gen cho bệnh nhân Wilson không chỉ là tiêu chuẩn vàng trong chẩn đoán xác định bệnh mà còn là cơ sở di truyền cần thiết để sàng lọc đột biến cho các thành viên khác trong gia đình.…”

Penicillamine-Related Lichenoid Dermatitis and Utility of Zinc Acetate in a Wilson Disease Patient with Hepatic Presentation, Anxiety and Spect Abnormalities

“…In conclusion, the present paper describes for the first time the appearance of lichenoid lesions after chronic penicillamine treatment in WD. Since most of WD penicillamine-treated patients do not seem to develop this skin lesion, it could be conceivable that a specific genetic factor can be involved in drug response other than in specific clinical presentation (35)(36)(37). Further studies are needed for a better clarification of WD therapy and in particular to differentiate specific therapies for different WD phenotypes.…”