title: Physical mapping of deletion breakpoints in patients with X-linked ichthyosis: evidence for clustering of distal and proximal breakpoints.
abstract: Previous studies have shown that approximately 80% of patients with X-linked ichthyosis have a total deletion of the steroid sulphatase (STS) locus which lies in Xp22.3-Xpter. We show by Southern analysis that a common core of sequences are absent in 78.6% of our cases, suggesting that the deletion breakpoints may be highly clustered. To characterize the region in more detail a long-range physical map of over 3 megabases (Mb) surrounding the STS locus was constructed using pulse-field gel electrophoresis. The map enabled the order of sequences tel-SI19-GMGXY3-[STS,GMGXY19]-GMGX9-[dic56 ,SIII2]-cen and the localization of the deletion breakpoints to be established. In ten cases the pulse-field evidence supports the clustering of breakpoints and indicates a deletion size of 2 Mb in most patients. Five CpG islands have been positioned around the STS locus and may be associated with other loci in the region involved in mental retardation and Kallman's syndrome. The map will be instrumental in an attempt to isolate and characterize the deletion breakpoints and to access other genes located in the region.
authors.affiliation: University of Cambridge, Department of Pathology, U.K.
authors.forename: R S
authors.initials: RS
authors.lastname: Newman
authors.forename: N A
authors.initials: NA
authors.lastname: Affara
authors.forename: J R
authors.initials: JR
authors.lastname: Yates
authors.forename: M
authors.initials: M
authors.lastname: Mitchell
authors.forename: M A
authors.initials: MA
authors.lastname: Ferguson-Smith
mesh_terms: D001192:Arylsulfatases / Q000172:deficiency / Q000235:genetics; D002872:Chromosome Deletion; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D007057:Ichthyosis / Q000201:enzymology / Q000235:genetics*; D015183:Restriction Mapping; D043266:Steryl-Sulfatase; D014960:X Chromosome
chemical_list: D001192:Arylsulfatases; D043266:Steryl-Sulfatase