ABCA12 is the major harlequin ichthyosis gene.
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.
Thomas
Anna C
AC
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.
Cullup
Tom
T
Norgett
Elizabeth E
EE
Hill
Tara
T
Barton
Stephanie
S
Dale
Beverly A
BA
Sprecher
Eli
E
Sheridan
Eamonn
E
Taylor
Aileen E
AE
Wilroy
Robert S
RS
DeLozier
Celia
C
Burrows
Nigel
N
Goodyear
Helen
H
Fleckman
Philip
P
Stephens
Karen G
KG
Mehta
Lakshmi
L
Watson
Rosemarie M
RM
Graham
Robert
R
Wolf
Roni
R
Slavotinek
Anne
A
Martin
Madelena
M
Bourn
David
D
Mein
Charles A
CA
O'Toole
Edel A
EA
Kelsell
David P
DP
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
C473801:ABCA12 protein, human; D018528:ATP-Binding Cassette Transporters; D018389:Codon, Nonsense