The chromosomal location and expression of SLC39A4, together with mutational analysis of eight families affected with acrodermatitis enteropathica, suggest that SLC39A4 is centrally involved in the pathogenesis of this condition.
The chromosomal location and expression of SLC39A4, together with mutational analysis of eight families affected with acrodermatitis enteropathica, suggest that SLC39A4 is centrally involved in the pathogenesis of this condition.
The chromosomal location and expression of SLC39A4, together with mutational analysis of eight families affected with acrodermatitis enteropathica, suggest that SLC39A4 is centrally involved in the pathogenesis of this condition.
In this article, we identify a gene, SLC39A4, located in the candidate region and, in patients with AE, document mutations that likely lead to the disease.
In this article, we identify a gene, SLC39A4, located in the candidate region and, in patients with AE, document mutations that likely lead to the disease.
About half of the missense AE-causing mutations occur within the large N-terminal extracellular domain (ECD), and our previous study has shown that ZIP4-ECD is crucial for optimal zinc uptake but the underlying mechanism has not been clarified.
The possible functional effect of the Leu372Val substitution, together with two pathological mutations at the same codon (Leu372Pro and Leu372Arg) that cause acrodermatitis enteropathica (a disease phenotype characterized by extreme zinc deficiency), was investigated by transient overexpression of human ZIP4 protein in HeLa cells.
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.
We also report the mutational analysis of human SLC30A4 in ten families with acrodermatitis enteropathica, which enabled us to exclude this gene from any involvement in the disorder of the patients examined.
We and others have recently identified the human gene encoding an intestinal zinc transporter of the ZIP family, SLC39A4, as the mutated gene in acrodermatitis enteropathica (AE).
We and others have recently identified the human gene encoding an intestinal zinc transporter of the ZIP family, SLC39A4, as the mutated gene in acrodermatitis enteropathica (AE).
Therefore, normal and AE fibroblasts were grown in normal medium containing physiological levels of Zn (16 micromol/L) for approximately 24 h. The medium was replaced by normal medium (16 micromol/L Zn), Zn-depleted medium (1.5 micromol/L Zn), or Zn-supplemented medium (200 micromol/L Zn) for another 24 h. Regardless of the Zn concentration of the growth medium, the AE fibroblasts contained significantly less Zn than normal fibroblasts grown in comparable medium.