Last update: 05/06/2006

Background to disease

OMIM # 308100

X-linked ichthyosis (XLI) is associated with deficiency of the microsomal enzyme steroid sulphatase deficiency. STS is capable of catalysing the hydrolysis of a variety of 3b-hydroxy steroid sulphates and is involved in the production of oestrogen from sulphated precursors during pregnancy. Affected individuals develop a brown scaly skin, most probably due to the build up of cholesterol sulphate.

The gene has been localised to Xp22.3 and a pseudogene on the long arm of the Y chromosome identified. The STS locus spans a region of 146kb and is organised in ten exons.

In more than 85% of patients with STS deficiency, a large deletion of the STS locus and its flanking sequences is responsible. The majority of patients appear to have the same deletion breakpoints, resulting in a deletion of approximately 2Mb. A number of ‘non deletion’ cases have been shown to be associated with point mutations.

Various complex syndromes, or contiguous gene syndromes have been found to be associated with microdeletions in the Xp22.3-Xpter region. A deletion panel constructed from such patients indicates that loci implicated in mental retardation (MRX) and chrondrodysplasia punctata (CDPX) lie distal to STS, whereas the Kallman’s syndrome (KAL) locus lies proximal.

Patients referred for testing are screened for deletions of the Xp22.3 region. The 6 markers used in the panel included sequences from the 5’ and 3’ ends of the STS gene and markers flanking the proximal and distal breakpoint of the ‘common’ deletion. These markers are multiplexed together in a single PCR.

The assay can be used to determine if patients with features of X-linked ichthyosis and mental retardation carry a large deletion resulting in a contiguous gene syndrome. Carrier testing of females is possible using FISH. These blood samples should be send to the cytogenetics laboratory in lithium heparin.

Laboratory Analysis

Contact scientist: Carol Delaney

	Test	Target reporting time (working days)
1.	Multiplex deletion screen (males only)	10