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Cell Tissue Res. 2013 Feb;351(2):281-8. doi: 10.1007/s00441-012-1474-9. Epub 2012 Aug 4.

Harlequin ichthyosis: ABCA12 mutations underlie defective lipid transport, reduced protease regulation and skin-barrier dysfunction.

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Centre for Cutaneous Research, Blizard Institute, Barts & The London School of Medicine and Dentistry, Queen Mary, University of London, London, E1 2AT, UK.


Harlequin ichthyosis (HI) is a devastating autosomal recessive congenital skin disease. It has been vital to elucidate the biological importance of the protein ABCA12 in skin-barrier permeability, following the discovery that ABCA12 gene mutations can result in this rare disease. ATP-binding cassette transporter A12 (ABCA12) is a member of the subfamily of ATP-binding cassette transporters and functions to transport lipid glucosylceramides (GlcCer) to the extracellular space through lamellar granules (LGs). GlcCer are hydrolysed into hydroxyceramides extracellularly and constitute a portion of the extracellular lamellar membrane, lipid envelope and lamellar granules. In HI skin, loss of function of ABCA12 due to null mutations results in impaired lipid lamellar membrane formation in the cornified layer, leading to defective permeability of the skin barrier. In addition, abnormal lamellar granule formation (distorted shape, reduced in number or absent) could further cause aberrant production of LG-associated desquamation enzymes, which are likely to contribute to the impaired skin barrier in HI. This article reviews current opinions on the patho-mechanisms of ABCA12 action in HI and potential therapeutic interventions based on targeted molecular therapy and gene therapy strategies.

[Indexed for MEDLINE]

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