Close linkage of the Wilsons's disease locus to D13S12 in the chromosomal region 13q21 and not to ESD in 13q14

Abstract

Wilson's disease (WD) is an autosomal recessive disorder resulting in copper accumulation notably in liver and brain tissue. Linkage of the WD locus (WND) to ESD at 13q14 was first shown by studies in families of Middle Eastern origin using the isozymic polymorphism of esterase D. Using RFLPs detected by the ESD cDNA we could not confirm this reported close linkage in an analysis of 17 WD families of northwest European origin. A tight linkage was detected, however, to the marker D13S12, located more distally at 13q21. No obligate cross-overs were detected in 63 gametes informative for this marker. Our data confirm an assignment of WND to 13q14-21. Its localization, however, seems to be more distal to ESD than previously reported. Although genetic heterogeneity cannot be excluded, the observed differences between the two populations are probably due to random variation.

A 4.5-megabase yeast artificial chromosome contig from human chromosome 13q14.3 ordering 9 polymorphic microsatellites (22 sequence-tagged sites) tightly linked to the Wilson disease locus.

“…Linkage of WND to this region in other populations has also been demonstrated by other groups (7)(8)(9).…”

The history of Wilson disease

“…In 1985, the chromosomal location of the locus linked to WD was reported [91] as being on chromosome 13 close to the locus for esterase D. In 1990, using restriction fragment length polymorphisms, the location was refined to between D13S31 and D13S55 of the q14-q21 band. [92] The next major advance (see Chelly et al [93] for review) was the cloning of the Menkes "Kinky hair" disease gene (ATP7A) early in 1993this being a condition in which copper absorption is defective, leading to copper deficiency and a range of serious consequences. [94] Later in 1993, 3 groups independently reported the cloning of the WD gene (ATP7B), 2 of whom used information from the Menkes disease gene, [95,96] whereas the third used a heavy metal binding motif from the amyloid β-protein precursor.…”

DNA‐based presymptomatic diagnosis of Wilson disease

“…We used probes from three loci in combination to study two families similar to earlier studies (Farrer et al, 1988;Yuzbasiyan-Gurkan et al, 1988;Houwen et al, 1990). The closest known marker (D13S26) is at a considerable genetic distance from the WND locus (7 cM) so, per generation, the two loci are linked 93% of the time (Figure 1).…”