Haplotype studies in Japanese patients with Wilson disease

Chromosomal haplotypes of six Japanese families with Wilson Disease (WND) were investigated with short tandem repeat (STR) polymorphisms at loci ; D13S314, D13S301 and D13S316. These markers had previously been established in northern European families and are all highly polymorphic and informative for the presymptomatic diagnosis for Japanese WND families as well. No statistically significant deviations in allele distributions between the normal and WND chromosomes were observed for either marker locus. However, two common haplotypes (combination of marker loci), D13S314-D13S301-D13S316: 11-2-7 and 11-3-7, were each more frequently observed in 4 out of 12 WND chromosomes. We then examined partial sequences of ATP7B (WND) gene where 41 disease-causing mutations were previously identified mainly in European populations. Two missense mutations, R779L and N1271S, were respectively identified in 1 out of 12 and 2 out of 12 Japanese WND chromosomes.