Novel point mutations in the steroid sulfatase gene in patients with X-linked ichthyosis: Transfection analysis using the mutated genes

X-linked ichthyosis is caused by steroid sulfatase deficiency which results from abnormalities in its coding gene. The majority of X-linked ichthyosis patients (approximate to 90%) have complete or partial deletions of the st eroid sulfatase gene. In this study, we examined the mutations of the stero id sulfatase gene in two unrelated X-linked ichthyosis patients without com plete deletion of the gene. Polymerase chain reaction-single-strand conform ation polymorphism and direct sequencing analyses showed that each patient has a different single base pair substitution within exon 8 encoding the C- terminal half of the steroid sulfatase polypeptide. Both mutations resulted in the transversion of functional amino acids: a G-->C substitution at nuc leotide 1344, causing a predicted change of a glycine to an arginine, and a C-->T substitution at nucleotide 1371, causing a change from a glutamine t o a stop codon. In vitro steroid sulfatase cDNA expression using site-direc ted mutagenesis revealed that these mutations are in fact pathogenic and re flect the levels of steroid sulfatase enzyme activities in each of the X-li nked ichthyosis patients.