Archives of Dermatological Research

, Volume 293, Issue 8, pp 392–396

Genomic localization, organization and amplification of the human zinc transporter protein gene, ZNT4, and exclusion as a candidate gene in different clinical variants of acrodermatitis enteropathica

Authors

  • Oliver Bleck
    • Department of Cell and Molecular Pathology, St John’s Institute of Dermatology, The Guy’s, King’s College, and St Thomas’ Hospitals’ Medical School, St Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, UK e-mail: john.mcgrath@kcl.ac.uk, Tel.: +44-20-79289292, Fax: +44-20-79228175
  • Gabrielle H. S. Ashton
    • Department of Cell and Molecular Pathology, St John’s Institute of Dermatology, The Guy’s, King’s College, and St Thomas’ Hospitals’ Medical School, St Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, UK e-mail: john.mcgrath@kcl.ac.uk, Tel.: +44-20-79289292, Fax: +44-20-79228175
  • Rajeev Mallipeddi
    • Department of Cell and Molecular Pathology, St John’s Institute of Dermatology, The Guy’s, King’s College, and St Thomas’ Hospitals’ Medical School, St Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, UK e-mail: john.mcgrath@kcl.ac.uk, Tel.: +44-20-79289292, Fax: +44-20-79228175
  • Andrew P. South
    • Department of Cell and Molecular Pathology, St John’s Institute of Dermatology, The Guy’s, King’s College, and St Thomas’ Hospitals’ Medical School, St Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, UK e-mail: john.mcgrath@kcl.ac.uk, Tel.: +44-20-79289292, Fax: +44-20-79228175
  • Neil V. Whittock
    • Epithelial Genetics Group, Department of Molecular and Cellular Pathology, Ninewells Medical School, Dundee, UK
  • W. H. Irwin McLean
    • Epithelial Genetics Group, Department of Molecular and Cellular Pathology, Ninewells Medical School, Dundee, UK
  • David J. Atherton
    • Department of Dermatology, The Hospital for Sick Children, Great Ormond Street, London, UK
  • J. A. McGrath
    • Department of Cell and Molecular Pathology, St John’s Institute of Dermatology, The Guy’s, King’s College, and St Thomas’ Hospitals’ Medical School, St Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, UK e-mail: john.mcgrath@kcl.ac.uk, Tel.: +44-20-79289292, Fax: +44-20-79228175
Original paper

DOI: 10.1007/s004030100246

Cite this article as:
Bleck, O., Ashton, G., Mallipeddi, R. et al. Arch Dermatol Res (2001) 293: 392. doi:10.1007/s004030100246

Abstract Acrodermatitis enteropathica is an inherited disorder of zinc metabolism, the molecular basis of which is currently unknown. Recent transgenic mouse studies have highlighted the potential significance of certain zinc transport proteins, for example ZnT4, in providing clues to the pathogenesis of zinc-related disorders such as acrodermatitis enteropathica. Specifically, mice of any genotype suckled on ZnT4-deficient mice fail to absorb intestinal zinc and ZnT4-deficient mice also develop dermatitis, alopecia and stunted growth. Therefore, to assess human ZnT4 as a candidate gene/protein in acrodermatitis enteropathica or related disorders, we characterized the intron-exon organization of the human ZNT4 gene, which comprises seven distinct exons spanning approximately 38.7 kb. High-resolution radiation hybrid mapping placed ZNT4 on 15q21.1. We also developed a PCR-based mutation detection strategy using primers placed on flanking introns followed by direct sequencing of the PCR products. Using this approach, we sequenced DNA from five individuals with acrodermatitis enteropathica; no mutations were identified. Thus, ZNT4 is unlikely to be the correct candidate gene for this disorder. We also identified and characterized two common single nucleotide polymorphisms in exon 5 and in the 3′ UTR of ZNT4, which will be useful for future genetic linkage studies in assessing ZNT4 as a candidate gene for other inherited disorders of zinc metabolism.

Keywords Acrodermatitis enteropathica Zinc ZNT4 gene

Copyright information

© Springer-Verlag Berlin Heidelberg 2001