STS Gene

The STS gene (STS stands for: steroid sulfatase) is a protein-coding gene located on chromosome Xp22.31 (short arm of the X chromosome).

Diseases associated with STS include:

• Ichthyosis X-linked (recessive) (XRI)

The STS gene encodes a membrane protein located in the endoplasmic reticulum. It belongs to the family of sulfatases and hydrolyzes various 3-beta-hydroxysteroid sulfates that serve as metabolic precursors for estrogens, androgens, and cholesterol. Thus, it catalyzes the conversion of sulfated steroid precursors such as dehydroepiandrosterone sulfate (DHEA-S) and estrone sulfate to the free steroid.

Mutations in this gene are associated with X-linked ichthyosis (XRI) in >90% of cases. These are complete deletions in 75% of cases and partial deletions of the STS gene in 25% (Cañueto J et al. 2010). These deletions lead to varying degrees of deficiency of microsomal steroid sulfatase. The result is elevations of cholesterol sulfate in keratinocytes, fibroblasts and leukocytes, among others.

The gene mutations may also extend to neighboring genes, leading to more complex disease associations.

For example, Hernández-Martín A et al (2010) reported a case of a patient who had both XRI and epidermolysis bullosa dystrophica. In this patient, a partial deletion in the STS gene and a recessive point mutation in the COL7A1 gene(encoding collagen 7A1) were detected.

Of note, X-linked recessive ichthyosis (XRI) is associated with attention deficit hyperactivity disorder(ADHD) (Brookes KJ et al. 2008; Stergiakouli E et al. 2011). The prevalence of ADHD is estimated to be 20-30% in XRI.

1. Brookes KJ et al (2008) Association of the steroid sulfatase (STS) gene with attention deficit hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet 147B:1531-1535.
2. Cañueto J et al (2010) Analysis of the STS gene in 40 patients with recessive X-linked ichthyosis: a high frequency of partial deletions in a Spanish population. J Eur Acad Dermatol Venereol 24:1226-1229.
3. Hernández-Martín A et al (2010) X-linked ichthyosis along with recessive dystrophic epidermolysis bullosa in the same patient. Dermatology 221:113-116.
4. Stergiakouli E et al. (2011) Steroid sulfatase is a potential modifier of cognition in attention deficit hyperactivity disorder. Genes Brain Behav 10:334-344.