title: Novel ATP7B mutations causing Wilson disease in several Israeli ethnic groups.
abstract: We characterized microsatellite marker haplotypes and identified mutations in members of 19 ethnically diverse Israeli families affected by Wilson disease (WD). Eighteen unique haplotypes were derived from allelic combinations for four marker loci spanning the WD gene, ATP7B, at chromosome 13q14.3: D13S133, D13S296, D13S301 and D13S295. Most of these haplotypes are population specific and vary among and even within different ethnic groups. Intrafamilial variability of WD haplotypes was observed in two large consanguineous families in which a single origin of WD was expected. In contrast, some WD haplotypes were identified in more than one group. Five novel and four previously described mutations were detected in our sample. The novel mutations include two deletions (845delT and 1639delC) and three missense mutations (E1064A, M645R, and G1213V). Mutations were identified for 11 of the 18 WD haplotypes, suggesting that other mutations may reside in noncoding regions of 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.
authors.affiliation: Department of Human Genetics, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv, Israel.
authors.forename: H
authors.initials: H
authors.lastname: Kalinsky
authors.forename: A
authors.initials: A
authors.lastname: Funes
authors.forename: A
authors.initials: A
authors.lastname: Zeldin
authors.forename: Y
authors.initials: Y
authors.lastname: Pel-Or
authors.forename: M
authors.initials: M
authors.lastname: Korostishevsky
authors.forename: R
authors.initials: R
authors.lastname: Gershoni-Baruch
authors.forename: L A
authors.initials: LA
authors.lastname: Farrer
authors.forename: B
authors.initials: B
authors.lastname: Bonne-Tamir
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D027682:Cation Transport Proteins; D000073840:Copper-Transporting ATPases; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006527:Hepatolenticular Degeneration / Q000235:genetics*; D006801:Humans; D007557:Israel / Q000208:ethnology; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D010375:Pedigree; D011110:Polymorphism, Genetic / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases