Figure 6.

Putative pathomechanism of harlequin ichthyosis. Based on our results, we propose a novel pathogenetic mechanism underlying harlequin ichthyosis (HI). Our results suggested that a lipid trafficking defect due to loss of ABCA12 function leads to not only malformation of the epidermal lipid barrier but also “an epidermal differentiation defect.” In our hypothesis, the severe hyperkeratosis, a characteristic phenotype of HI skin, is not a hyperkeratosis compensating for any barrier insufficiency, but a hyperkeratosis due to both defective differentiation and an abnormal desquamation process. The present scenario explains both the HI skin phenotype at/after birth and even in utero.