HIGH-FREQUENCY OF 2 MUTATIONS IN CODON-778 IN EXON-8 OF THE ATP7B GENE IN TAIWANESE FAMILIES WITH WILSON-DISEASE

The gene for Wilson disease (WD) has been cloned as a P type copper tr ansporter gene (ATP7B). To elucidate the possible genetic mechanism fo r the diversity of clinical manifestations, we characterised 22 Taiwan ese families with WD by microsatellite haplotyping of close DNA marker s D13S314-D13S301-D13S316. We also screened for mutations of codon 778 in the transmembrane region. There were at least 15 haplotypes within eight broad subgroups observed among 44 WD chromosomes. Among the 22 unrelated patients, we found that six patients (27%) carried a codon 7 78 mutation. Nucleotide sequence analysis showed there were two differ ent mutations: the previously reported Arg778Leu mutation in four pati ents and Arg778Gln, a new mutation, in two patients. The two different mutations of the same codon occurred in two distinct microsatellite h aplotypes.