Somatic and germinal mosaicism for the steroid sulfatase gene deletion in a steroid sulfatase deficiency carrier.

Steroid sulfatase deficiency results in X-linked ichthyosis, an inborn error of metabolism in which the principal molecular defect is the complete deletion of the steroid sulfatase gene and flanking markers. Mosaicism for the steroid sulfatase gene has not yet been reported in X-linked ichthyosis. In this study we describe an X-linked ichthyosis patient with complete deletion of the steroid sulfatase gene and his mother with somatic and germinal mosaicism for this molecular defect. The family (X-linked ichthyosis patient, grandmother, mother, and sister) was analyzed through steroid sulfatase enzyme assay, polymerase chain reaction, DNA markers, and fluorescence in situ hybridization of the steroid sulfatase gene. Steroid sulfatase activity was undetectable in the X-linked ichthyosis patient, very low in the mother, and normal in the grandmother and sister. The X-linked ichthyosis patient showed a 2 Mb deletion of the steroid sulfatase gene and flanking regions from 5'DXS1139 to 3'DXF22S1. The mother showed one copy of the steroid sulfatase gene in 98.5% of oral cells and in 80% of leukocytes. The grandmother and sister showed two copies of the steroid sulfatase gene. The origin of the X chromosome with the deletion of the steroid sulfatase gene corresponded to the grandfather of the proband. We report the first case of somatic and germinal mosaicism of the steroid sulfatase gene in an X-linked ichthyosis carrier and propose DNA slippage as the most plausible mechanism in the genesis of this mosaicism.