title: ABCA12 is the major harlequin ichthyosis gene.
abstract: 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.
authors.affiliation: Centre for Cutaneous Research, Institute of Cell and Molecular Science, Queen Mary's School of Medicine and Dentistry, Queen Mary, University of London, London, UK.
authors.forename: Anna C
authors.initials: AC
authors.lastname: Thomas
authors.forename: Tom
authors.initials: T
authors.lastname: Cullup
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Norgett
authors.forename: Tara
authors.initials: T
authors.lastname: Hill
authors.forename: Stephanie
authors.initials: S
authors.lastname: Barton
authors.forename: Beverly A
authors.initials: BA
authors.lastname: Dale
authors.forename: Eli
authors.initials: E
authors.lastname: Sprecher
authors.forename: Eamonn
authors.initials: E
authors.lastname: Sheridan
authors.forename: Aileen E
authors.initials: AE
authors.lastname: Taylor
authors.forename: Robert S
authors.initials: RS
authors.lastname: Wilroy
authors.forename: Celia
authors.initials: C
authors.lastname: DeLozier
authors.forename: Nigel
authors.initials: N
authors.lastname: Burrows
authors.forename: Helen
authors.initials: H
authors.lastname: Goodyear
authors.forename: Philip
authors.initials: P
authors.lastname: Fleckman
authors.forename: Karen G
authors.initials: KG
authors.lastname: Stephens
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Mehta
authors.forename: Rosemarie M
authors.initials: RM
authors.lastname: Watson
authors.forename: Robert
authors.initials: R
authors.lastname: Graham
authors.forename: Roni
authors.initials: R
authors.lastname: Wolf
authors.forename: Anne
authors.initials: A
authors.lastname: Slavotinek
authors.forename: Madelena
authors.initials: M
authors.lastname: Martin
authors.forename: David
authors.initials: D
authors.lastname: Bourn
authors.forename: Charles A
authors.initials: CA
authors.lastname: Mein
authors.forename: Edel A
authors.initials: EA
authors.lastname: O'Toole
authors.forename: David P
authors.initials: DP
authors.lastname: Kelsell
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D017490:Ichthyosis, Lamellar / Q000235:genetics*; D008297:Male; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D017384:Sequence Deletion
chemical_list: C473801:ABCA12 protein, human; D018528:ATP-Binding Cassette Transporters; D018389:Codon, Nonsense