Molecular studies of deletions at the human steroid sulfatase locus.

Abstract

The human steroid sulfatase gene (STS) is located on the distal X chromosome short arm close to the pseudoautosomal region but in a segment ofDNA that is unique to the X chromosome. In contrast to most X chromosomeencoded genes, STS expression is not extinguished during the process of X chromosome inactivation. Deficiency of STS (steryl-sulfatase; steryl-sulfate sulfohydrolase, EC 3.1.6.2) activity produces the syndrome of X chromosome-linked ichthyosis, which is one of the most common inborn errors of metabolism in man. Approximately 90% of STS-individuals have large deletions at the STS locus. We and others have found that the end points of such deletions are heterogeneous in their location. One recently ascertained subject was observed to have a 40-kilobase deletion that is entirely intragenic, permitting the cloning and sequencing of the deletion junction. Studies of this patient and of other X chromosome sequences in other subjects permit some insight into the mechanism(s) responsible for generating frequent deletions on the short arm of the X chromosome.

Recombination by sequence repeats with formation of suppressive or residual mitochondrial DNA in Neurospora.

“…The same mechanism is believed to generate deletions at nuclear loci in many organisms, including mammals; better characterized are the hypoxanthine phosphoribosyltransferase, adenine phosphoribosyltransferase, retinoblastoma, Duchenne muscular dystrophy, or steroid sulfatase loci (32)(33)(34)(35). In addition, integration and excision of mammalian viruses like simian virus 40 or polyomavirus (36) as well as DNA amplification in the mammalian system (37) are believed to take place by the same mechanism.…”

The Biological Roles of Steroid Sulfonation

“…Most cases (≈80-90%) are caused by complete deletion of the STS gene, whereas small deletions or point mutations account for the remainder of cases [56]. Loss of STS leads to an accumulation (up to 20-fold increase) of its substrate, cholesterol sulfate, in plasma and red cell membranes, as well as the epidermis [57].…”

Effects of mutations and glycosylations on STS activity: A site-directed mutagenesis study

“…The STS cDNA was kindly provided by Dr Stein and Dr Shapiro (Shapiro et al, 1989;Stein et al, 1989). A c c e p t e d M a n u s c r i p t 6 glycerol and 1 mM PMSF).…”

“…Inactivation of the STS gene results in X-linked ichthyosis (XLI), one of the most prevalent human inherited errors of metabolism (Shapiro et al, 1989). In 80-90% of cases, the XLI is due to complete deletion of the 146 kb STS gene and substantial flanking regions from the distal Page 4 of 23 A c c e p t e d M a n u s c r i p t 4 short arm of the X chromosome.…”