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MOLECULAR DIAGNOSIS FOR WILSON DISEASE IN JAPAN

Shimizu N¹⁾, Takeshita Y¹⁾, Nakazono H¹⁾, Watanabe A¹⁾, Hemmi H²⁾,

Shimatake H²⁾, Aoki T¹⁾

¹⁾ 2nd Department of Pediatrics, Toho University School of Medicine, Ohashi Hospital

²⁾ Department of Molecular Biology, Toho University School of Medicine, Japan

Introduction: Wilson disease is an autosomal recessive disorder, characterized by the toxic accumulation of copper in the liver, brain, cornea and other organs. The Wilson disease gene (ATP7B) has been cloned as a putative copper-transporting P-type ATPase gene. We therefore analyzed mutations of ATP7B in Japanese patients with Wilson disease and establish a molecular diagnosis system.

Methods: Thirty independent Japanese patients with Wilson disease and one family (parents and siblings) were investigated. The mutations of ATP7B gene were detected by direct sequencing analy sis for genomic PCR products and/or RT-PCR products.

Results: Sixteen mutations were identified, including ten missense mutations, four deletions, one insertion and one exon skipping in the coding region. The most common mutation was Arg778Leu in exon 8, and next was 2871 deletion Cin exon 13.

Discussion: None of the observed mutations, except for 2299 insertion C, Asp 765 Asn and Asn1270Ser, have been previously detected in either European and North American patients. We conclude that the mutation spectrum of Wilson disease may indicate a population-dependent pattern. Thus based on the population-dependent strategy of the occurrence of ATP7B gene mutation, it may be possible to establish a molecular diagnosis system for Wilson disease. A molecular diagnosis is considered to be very effective for making non-invasive diagnosis and for also detecting carriers.