HARLEQUIN ICHTHYOSIS - VARIABILITY IN EXPRESSION AND HYPOTHESIS FOR DISEASE MECHANISM

Background: Harlequin ichthyosis is an inherited skin disorder that us ually results in death shortly after birth. Although the clinical feat ures of this disorder are well described, the underlying molecular bas is is not understood. in this article, we discuss the results of the l atest histologic, immunochemical, and Western immunoblotting studies d one in our laboratory and propose a hypothesis for molecular basis of this disorder. Observations: Previous experiments done in our laborato ry show suggestive evidence for defective lipid synthesis and protein dephosphorylation in harlequin ichthyosis. Our latest study shows that the catalytic subunit of one of the most prevalent protein phosphatas e, type 2A protein phosphatase, appears to be altered in some cases of type 2 harlequin ichthyosis. Conclusions: Based on these observations and the known functions of protein phosphatase in keratinocytes, we h ypothesize that the underlying molecular basis of harlequin ichthyosis may be related to mutations affecting protein dephosphorylation. We f urther describe approaches by which this hypothesis can be tested.