Identification of a unique splice site variant in SLC39A4 in bovine hereditary zinc deficiency, lethal trait A46: An animal model of acrodermatitis enteropathica.

Lethal trait A46, also known as bovine hereditary zinc deficiency, Adema disease, and hereditary parakeratosis, is an autosomal recessive disorder first described in 1964, with a clinical presentation similar to that of acrodermatitis enteropathica (AE) in humans. The molecular basis of the defect has not been previously identified. Recently, the basic defect in AE was found to lie in SLC39A4. We report the characterization of the bovine ortholog of SLC39A4 and identification of a unique splice site variant within this gene in affected animals. The mutation leads to exon skipping, leaving the coding region in frame. The gene product is predicted to lack two critical motifs, which lie in adjacent transmembrane domains implicated in the formation of a pore responsible for the transport of zinc. While further functional studies are warranted, this unique variant is likely to be responsible for the impaired zinc absorption in this disease.