ABCA12 is the major harlequin ichthyosis gene

Anna C. Thomas, Tom Cullup, Elizabeth E. Norgett, Tara Hill, Stephanie Barton, Beverly A. Dale, Eli Sprecher, Eamonn Sheridan, Aileen E. Taylor, Robert S. Wilroy, Celia DeLozier, Nigel Burrows, Helen Goodyear, Philip Fleckman, Karen G. Stephens, Lakshmi Mehta, Rosemarie M. Watson, Robert Graham, Roni Wolf, Anne SlavotinekMadelena Martin, David Bourn, Charles A. Mein, Edel A. O'Toole, David P. Kelsell*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Harlequin ichthyosis (HI) is the most severe form of autosomal-recessive, congenital ichthyosis. Affected infants have markedly impaired barrier function and are more susceptible to infection. Abnormalities in the localization of epidermal lipids as well as abnormal lamellar granule formation are features of HI skin. Previously, we and others have shown that mutations in the ABCA12 gene encoding an adenosine triphosphate-binding cassette (ABC) transporter underlie the skin disease HI. In this study, we have sequenced the ABCA12 gene in an additional 14 patients and show that all contain mutations, with the majority being either nonsense substitution or frameshift mutations. Eleven HI patients had bi-allelic ABCA12 mutations, whereas in the remaining three HI patients in this study, ABCA12 mutations were detected on only one allele by sequencing. In addition, the one patient from the previous study where no sequence mutations were detected was screened for heterozygous deletions. A combination of oligonucleotide arrays, multiplex PCR analysis and single-nucleotide polymorphism genotyping revealed a heterozygous intragenic deletion in exon 8. These mutation data establish ABCA12 as the major HI gene.

Original languageEnglish
Pages (from-to)2408-2413
Number of pages6
JournalJournal of Investigative Dermatology
Issue number11
StatePublished - 15 Nov 2006
Externally publishedYes


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