The role of MBTPS2 in epidermal proliferation and differentiation -

Abstract

Ichthyosis (“fish scales”) and ichthyosiform disorders are inherited skin disorders for which no ideal therapy exists. These disorders are mainly caused by disturbances in epidermal differentiation and can present either as isolated skin diseases or as part of syndromes. Clinically, there is a spectrum of phenotypic features ranging from mild skin dryness to complete disruption of the skin barrier resulting in severe complications and death at times.Advances in molecular techniques in the past few years played a substantial role in the identification of genetic alterations involved in the pathogenesis of ichthyosis-ichthyosiform disorders. We have recruited multiple families with different types of ichthyosis-ichthyosiform disorders during the past four years. We identified several mutations in different genes related to these disorders. MBTPS2 is a gene mutated in ichthyosis follicularis with atrichia and photophobia (IFAP). The function of MBTPS2 in epidermal physiology is unknown.IFAP syndrome is a severe form of syndromic ichthyosis, which is clinically characterized by nonscarring hair loss, hyperkeratotic psoriasiform plaques, follicular ichthyosis, photophobia and at times ectrodactyly. Therefore, IFAP syndrome at the molecular level could have disturbances in epidermal proliferation and differentiation. Among the major pathways involved in proliferation is Tp63, which is also associated with syndromes involving ectrodactyly when mutated. On the other hand, NOTCH and the more recently investigated matriptase, are involved in skin differentiation. In this study, we investigated whether and how MBTPS2 is involved in the processes of epidermal proliferation and differentiation under normal and disease processes.