NOVEL ATP7B MUTATIONS CAUSING WILSON-DISEASE IN SEVERAL ISRAELI ETHNIC-GROUPS

We characterized microsatellite marker haplotypes and identified mutat ions in members of 19 ethnically diverse Israeli families affected by Wilson disease (WD). Eighteen unique haplotypes were derived from alle lic combinations for four marker loci spanning the WD gene, ATP7B, at chromosome 13q14.3: D13S133, D13S296, D13S301 and D13S295. Most of the se haplotypes are population specific and vary among and even within d ifferent ethnic groups. Intrafamilial variability of WD haplotypes was observed in two large consanguineous families in which a single origi n of WD was expected. In contrast, some WD haplotypes were identified in more than one group. Five novel and four previously described mutat ions were detected in our sample, The novel mutations include two dele tions (845delT and 1639delC) and three missense mutations (E1064A, M64 5R, and G1213V). Mutations were identified for 11 of the 18 WD haploty pes, suggesting that other mutations may reside in noncoding regions o f the ATP7B gene. Identification of all WD mutations will undoubtedly increase our understanding of the normal function of ATP7B as well as lead to more accurate prognosis and genetic counseling. (C) 1998 Wiley -Liss, Inc.