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Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis

David P Kelsell1, Elizabeth E Norgett, Harriet Unsworth

  • 1Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, London, United Kingdom. d.p.kelsell@qmul.ac.uk

American Journal of Human Genetics
|March 10, 2005
PubMed

Insights

Mutations in the ABCA12 gene cause Harlequin ichthyosis (HI), a severe skin barrier disorder. This discovery enables prenatal diagnosis and advances understanding of skin development.

Area of Science:

  • Genetics
  • Dermatology
  • Molecular Biology

Background:

  • Harlequin ichthyosis (HI) is a severe, often lethal, congenital skin disorder.
  • The genetic cause of HI and its cellular basis remain largely unknown.
  • Previous research suggested defects in lipid transport and cell differentiation.

Purpose of the Study:

  • To identify the genetic basis of Harlequin ichthyosis.
  • To investigate the role of specific genes in HI pathogenesis.
  • To explore the implications for diagnosis and understanding skin barrier formation.

Main Methods:

  • Homozygosity mapping using single-nucleotide-polymorphism chip technology in HI patients.
  • Sequencing of the ABCA12 gene located in the identified homozygous chromosomal region.
  • Analysis of mutations including deletions and frameshift mutations.

Main Results:

  • A common region of homozygosity at chromosomal location 2q35 was identified in five HI patients.
  • Disease-associated mutations, including large intragenic and frameshift deletions in the ABCA12 gene, were found in 11 out of 12 HI individuals.
  • ABCA12 mutations correlate with abnormal lamellar granule formation in HI epidermis.

Conclusions:

  • The ABCA12 gene is implicated in the pathogenesis of Harlequin ichthyosis.
  • ABCA12 mutations disrupt lipid discharge and epidermal barrier formation.
  • This finding supports early prenatal diagnosis and further research into epidermal differentiation.

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