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Updated: Jun 29, 2025

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
Cardiac arrhythmia in individuals with steroid sulfatase deficiency (X-linked ichthyosis): candidate anatomical and
Georgina H Wren1, William Davies1,2,3
1School of Psychology, Cardiff University, Cardiff, U.K.
Abstract:
Circulating steroids, including sex hormones, can affect cardiac development and function. In mammals, steroid sulfatase (STS) is the enzyme solely responsible for cleaving sulfate groups from various steroid molecules, thereby altering their activity and water solubility. Recent studies have indicated that Xp22.31 genetic deletions encompassing STS (associated with the rare dermatological condition X-linked ichthyosis), and common variants within the STS gene, are associated with a markedly elevated risk of cardiac arrhythmias, notably atrial fibrillation/flutter. Here, we consider emerging basic science and clinical findings which implicate structural heart abnormalities (notably septal defects) as a mediator of this heightened risk, and propose candidate cellular and biochemical mechanisms. Finally, we consider how the biological link between STS activity and heart structure/function might be investigated further and the clinical implications of work in this area.
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