Histochemical and electron microscopic studies on the skin disease keratoderma hereditaria mutilans (Vohwinkel's syndrome) /

Abstract

Keratoderma Hereditaria Mutilans (KHM) or Vohwinkel's Syndrome is a rare autosomal dominant skin disease characterized primarily by diffuse hyperkeratosis of both the palmar and the plantar regions of the skin. Other prominent features include an increase in the thickness of the stratum corneum layer of the epidermis, coupled with, an increase in the levels of ~-glucuronidase enzyme in both serum and urine. It has now been established that Vohwinkel' s Syndrome is a direct result of a defect found in the gene encoding a structural protein located within the cornified cellular envelope of the skin. This protein is known as loricrin. The exact chromosomal location of the specific loricrin gene was found to be in the Iq2l position, mapped within the epidermal differentiation complex (EDC). It is believed that a frameshift mutation within the loricrin gene causes a significant decrease in the flexibility of the cornified cell envelope layer by impairing and disrupting its ability to properly crosslink loricrin thereby contributing to an impairment in barrier function causing patients with Vohwinkel' s Syndrome to retain water within the keratinocytes. This research focuses on the exact nature of KHM with an emphasis on both transmission and scanning electron microscopy techniques, in addition to histochemical staining of epidermal tissues using various techniques. Immunohistochemical methodologies were employed for the identification and localization of the loricrin protein. Furthermore, experimental studies were performed to investigate and determine the specific role the B-glucuronidase enzyme plays in this disorder by quantitatively determining the level of B-glucuronidase and its localization throughout the layers of the epidermis via specific enzymatic assays. The use of electron microscopy in this study provided a vital technique in which Vohwinkel's Syndrome was closely examined to reveal many insights into the nature and cause of this disease.