Background: Steroid sulphatase (STS) deficiency has been described in a diversity of ethnic populations. The phenotype of STS deficiency, X-linked ichthyosis (XLI), is a genodermatosis characterized by dark scaly skin. About 90% of patients with XLI have complete deletion of the entire STS gene and flanking sequences. The variable number tandem repeats, on either side of the STS gene, appear to play an important role in these interstitial deletions due to nonallelic homologous recombination (NAHR). It is difficult to establish if this NAHR occurs between two chromosomes, between sister chromatids or between the same chromatid.
Objectives: To identify the parental origin of the affected X-chromosome in seven unrelated sporadic cases of XLI.
Methods: Amplification of the regions from DXS89 to DXS1134 (telomeric-centromeric) including the 5' and 3' ends of the STS gene was performed through polymerase chain reaction. GeneScan analysis was performed using the DXS987, DXS8051 and DXS1060 markers located on the short arm of the X-chromosome. Fluorescence in situ hybridization analysis was performed with a digoxigenin-labelled cDNA STS probe.
Results: STS gene deletion in patients with XLI involved the sequences DXS1139 and DXF22S1. In five families segregation analysis showed paternal transmission of the affected X-chromosome in the XLI carrier. It was not possible to determine the parental origin of the affected X-chromosome in two families.
Conclusions: These data strongly suggest that STS gene deletion occurred in the male meiosis probably due to an intrachromosomal event, recombination between S232 sequences on the same DNA molecule, or during the process of DNA replication.