Mutation analysis of Wilson disease in Taiwan and description of six new mutations

Abstract

Wilson disease is an autosomal recessive disorder of copper metabolism. Mutation screening in Wilson disease has led to the detection of at least 89 disease‐specific mutations. Some mutations appear to be population specific, while others are common to many populations. In this study, 38 Taiwanese patients with Wilson disease were screened using single‐strand conformation polymorphism analysis, followed by direct DNA sequencing. We found 12 different mutations, six of which were novel. All our detected mutations were found to be in eight exons. Four mutations in three loci (Arg778Gln, Arg778Leu, Gly943Asp, and Pro992Leu) accounted for about 58% of the mutant alleles we detected. Using an RNA transcriptional assay, we confirmed that both of our detected splice‐site mutations resulted in exon skipping. Hum Mutat 12:370–376, 1998. © 1998 Wiley‐Liss, Inc.

Molecular analysis of Wilson disease in Taiwan: identification of one novel mutation and evidence of haplotype-mutation association

“…Besides the 12 mutations previously reported by Tsai et al (1998), we identified another 4 missense mutations (A874V, V1216M, E1173K, and D1279G) in Taiwanese WND chromosomes; the A874V mutation was recently reported in Japanese and Korean WND chromosomes (Yamaguchi et al 1998;Kim et al 1998), and V1216M and E1173K were identified in Mediterranean WND chromosomes (Loudianos et al 1998(Loudianos et al , 1999. However, D1279G is a novel mutation with nonconservative amino acid substitution.…”

“…We had previously identified 12 different mutations in 70% Taiwanese WND chromosomes analyzed (Tsai et al 1998). We, herein, report the finding of another 4 missense mutations, 1 of which is novel.…”

“…Among these identified WND mutations, we observed haplotypemutation association among most mutations. The G943D mutation, which was reported only in Taiwanese WND patients (Tsai et al 1998), was found exclusively associated with the 11-1.5-5.5 haplotype (n ϭ 7). R778L, the most frequently found WND mutation in Taiwanese, was associated with either 8-4-4 (n ϭ 4) or 8-4-5.5 (n ϭ 4).…”

“…Mutation analysis had previously been performed in 25 of these 31 WND patients (Tsai et al 1998), while 6 patients were newly referred to this study. Genomic DNA was prepared from the peripheral blood using a DNA Extractor WB kit (Wako, Tokyo, Japan).…”

“…Mutation analysis of the ATP7B gene Exons 1-21 of ATP7B were polymerase chain reaction (PCR) amplified and were subjected to mutation analysis by single-strand conformation polymorphism (SSCP), using a GenePhor DNA Electrophoresis System (Pharmacia, Uppsala, Sweden) following the protocol described by Tsai et al (1998). Exons that exhibited an irregular shift by SSCP were subjected to direct sequencing for mutation identification.…”