Carrier identification by FISH analysis in isolated cases of X-linked ichthyosis

X-linked ichthyosis (XLI) is an inborn error of metabolism due to steroid s ulfatase (STS) deficiency. STS assay and FISH are useful in diagnosing carr ier status of XLI. Biochemical analysis appears to indicate that most spora dic cases are inherited. Since this method does not seem to be completely r eliable in recognizing XLI-carriers, the aim of the present study was to co rroborate by FISH whether or not most sporadic cases of XLI had de novo mut ations. XLI patients were classified through STS assay and PCR amplificatio n of 5 ' -3 ' ends of the STS gene. XLI patients had undetectable levels of STS activity and complete deletion of the STS gene. Patients' mothers were studied through STS assay and FISH. Nine out of 12 mothers presented an ST S activity compatible with XLI-carrier state. These mothers also had only o ne copy of the STS gene, indicating that they carry the primary gene defect . One mother had normal STS activity but only one copy of the STS gene. Thi s data corroborated that most sporadic cases do not represent de novo mutat ions, and that FISH must be included in the analysis of mothers of sporadic cases when they present with normal STS activity, in order to correctly di agnose the XLI carrier state. (C) 2001 Wiley-Liss, Inc.