title: Linkage of the Wilson disease gene to chromosome 13 in North-American pedigrees.
abstract: Wilson disease (WD) is an autosomal recessive disorder resulting in copper accumulation to toxic levels. Patients may present with neurologic, hepatic, or hematologic disease at any age between the first and fifth decade of life. Because of clinical heterogeneity, genetic heterogeneity in the etiology of the disease has been proposed. Recently, linkage of the WD locus to loci on 13q has been demonstrated in five Middle-Eastern kindreds. We have used esterase D and several polymorphic markers on 13q to investigate linkage in WD pedigrees from the United States and Canada. Ten kindreds, three with hepatic and seven with neurologic presentations, were informative, yielding a lod score of 2.189 at a recombination fraction of .06 with probe 7F12 at D13S1. Patients were generally of mixed European background, but one particularly informative pedigree was Hispanic. Our data confirm the provisional assignment of the gene for WD to 13q. More specifically, our findings indicate that, irrespective of ethnic background or clinical presentation, the linkage to 13q will be present in most pedigrees. The relative lack of linkage heterogeneity indicates that closely linked polymorphic loci on 13q can be useful in prenatal and presymptomatic diagnosis and in heterozygote detection.
authors.affiliation: Department of Human Genetics, University of Michigan Medical School, Ann Arbor 48109-0618.
authors.forename: V
authors.initials: V
authors.lastname: Yuzbasiyan-Gurkan
authors.forename: G J
authors.initials: GJ
authors.lastname: Brewer
authors.forename: E
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: P J
authors.initials: PJ
authors.lastname: Venta
mesh_terms: D000293:Adolescent; D000328:Adult; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000235:genetics; D002882:Chromosomes, Human, Pair 13; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D006527:Hepatolenticular Degeneration / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree; D011110:Polymorphism, Genetic
chemical_list: D005819:Genetic Markers; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase; C020118:ESD protein, human