1. ¹Epithelial Genetics Group, Human Genetics Unit, Division of Pathology and Neuroscience, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
2. ²Department of Dermatology, Tayside University Hospitals NHS Trust, Ninewells Hospital and Medical School, Dundee, UK
3. ³Department of Clinical Genetics, Tayside University Hospitals NHS Trust, Ninewells Hospital and Medical School, Dundee, UK
4. ⁴Department of Biochemical Genetics, Institute of Medical Genetics, Yorkhill Hospitals, Glasgow, UK

Correspondence: Professor W. H. Irwin McLean, Human Genetics Unit, Ninewells Medical School, Dundee DD1 9SY, UK. E-mail: w.h.i.mclean@dundee.ac.uk

Received 12 March 2007; Revised 9 April 2007; Accepted 13 April 2007; Published online 26 July 2007.

Abstract

Mutations inactivating the STS gene cause X-linked ichthyosis (XLI), whereas null mutations in the FLG gene cause ichthyosis vulgaris. Two brothers presented with XLI. One had a typical fine scaling, and the other was much more severely affected. Both patients carried STS missense mutation T165I. Furthermore, the more severely affected patient also carried heterozygous FLG mutation R501X, which was absent from his mildly affected brother. These data suggest that disrupting epidermal differentiation via different pathways can increase phenotypic severity. Owing to the high population frequency of FLG mutations, filaggrin is a possible genetic modifier in other genodermatoses.