@article{d3673bb184c54ba08183b49037959549,
title = "Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis",
abstract = "Harlequin ichthyosis (HI) is the most severe and frequently lethal form of recessive congenital ichthyosis. Although defects in lipid transport, protein phosphatase activity, and differentiation have been described, the genetic basis underlying the clinical and cellular phenotypes of HI has yet to be determined. By use of single-nucleotide-polymorphism chip technology and homozygosity mapping, a common region of homozygosity was observed in five patients with HI in the chromosomal region 2q35. Sequencing of the ABCA12 gene, which maps within the minimal region defined by homozygosity mapping, revealed disease-associated mutations, including large intragenic deletions and frameshift deletions in 11 of the 12 screened individuals with HI. Since HI epidermis displays abnormal lamellar granule formation, ABCA12 may play a critical role in the formation of lamellar granules and the discharge of lipids into the intercellular spaces, which would explain the epidermal barrier defect seen in this disorder. This finding paves the way for early prenatal diagnosis. In addition, functional studies of ABCA12 will lead to a better understanding of epidermal differentiation and barrier formation.",
author = "Kelsell, {David P.} and Norgett, {Elizabeth E.} and Harriet Unsworth and Teh, {Muy Teck} and Thomas Cullup and Mein, {Charles A.} and Dopping-Hepenstal, {Patricia J.} and Dale, {Beverly A.} and Gianluca Tadini and Philip Fleckman and Stephens, {Karen G.} and Sybert, {Virginia P.} and Mallory, {Susan B.} and North, {Bernard V.} and Witt, {David R.} and Eli Sprecher and Taylor, {Aileen E.M.} and Andrew Ilchyshyn and Kennedy, {Cameron T.} and Helen Goodyear and Celia Moss and David Paige and Harper, {John I.} and Young, {Bryan D.} and Leigh, {Irene M.} and Eady, {Robin A.J.} and O'Toole, {Edel A.}",
note = "Funding Information: The authors acknowledge the patients and their families who have contributed to the study. In addition, we acknowledge the contributions of Drs. Nick Lench and Sarah Hatsell during the early stages of our genetic studies of HI; Tracy Chaplin, who runs the SNP Array facility at Queen Mary; and Drs. Sandra Charles-Holmes (Coventry), Vinnie Biggs (Holyoke, MA), Michael Heffernan (St. Louis), and Richard Mupanemunda (Birmingham), for assistance with the clinical aspects of this study. We also acknowledge the major contribution of Dr. Karen Holbrook (Columbus, OH) to our understanding of the pathogenesis of HI. Funding was from the Wellcome Trust (to R.A.J.E.), a Wellcome Trust Prize Studentship (to E.E.N.), United States Public Health Service grant 2P01 AR 21557 (to P.F.), the Odland Endowed Research Fund (to P.F.), and the Barts and The London Charitable Foundation (to B.D.Y.). ",
year = "2005",
month = may,
doi = "10.1086/429844",
language = "אנגלית",
volume = "76",
pages = "794--803",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "5",
}