POSTER NO: 322

Haplotype and R778L Mutation Analysis in Chinese Patients with Wilson Disease

Xiao-qing Liu, Xue-fan Gu, Ya-fen Zhang, Ke-rong Bao
Xin Hua Hospital, Shanghai Second Medical University and Shanghai Institute for Pediatric Research, China, 1665 Kongjiang Rd., Shanghai, China

Wilson disease (WD), an autosomal recessive disorder of copper transport, is characterized by biliary excretion and by impaired incorporation of copper into ceruloplasmin. Toxic accumulation of copper causes tissue damage, primarily in the liver, brain, and kidneys. Here, haplotype analysis using three microsatellite markers, D13S314, D13S301, and D13S316, has been a useful indicator of specific mutations. Based on the analysis of haplotypes of D13S314, D13S301and D13S316, size of segments was 134-157bp, 128-156 bp, and 136-154 bp, 19, 20, and 15 alleles were obtained in 65 patients unrelated WD families from China, 123 carriers and 54 normal persons respectively. Heterozygosity was 0.79, 0.82, and 0.23. In this study, seventy-two different haplotypes were observed on 130 WD chromosomes. Haplotype 12-6-5, 15-10-5, 6-10-5 and 6-15-5, the commonest haplotypes. In all the patients, the exon 8 of ATP7B coding sequece was screened for mutations of 778 region, by SSCP and Msp I restriction enzyme, followed by direct-sequence analysis of the shifted fragments. We identified R778L mutations in 36 WD patients, found associated with haplotype 6-9-5 (n=3 ), 12-9-5(n=4), 12-6-5 (n=3), 12-8-5(=4), 6-14-5(=3) and 6-10-5(=3).