A Mutation in the Gene in Dogs with Hereditary Footpad Hyperkeratosis (HFH)

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The palms and soles of mammals are covered by the palmoplantar epidermis, which has to bear immense mechanical forces and has therefore a special composition in comparison to the epidermis on regular skin. We studied a Mendelian disease in dogs, termed hereditary footpad hyperkeratosis (HFH). HFH affected dogs develop deep fissures in the paw pads, which are the consequence of a pathological thickening of the outermost layer of the epidermis. We mapped the disease causing genetic variant in the Kromfohrländer and Irish Terrier breeds to a 611 kb interval on chromosome 5. HFH affected Kromfohrländer and Irish Terriers shared the same haplotype indicating descent from a common founder. We re-sequenced the genome of an affected dog and compared it to genome sequences of 46 control dogs. The HFH affected dog had only one private non-synonymous variant in the critical interval, a missense variant of the FAM83G gene. We genotyped this variant in more than 500 dogs and found perfect association with the HFH phenotype. Our data very strongly suggest that the FAM83G variant is causative for HFH. FAM83G is a protein with unknown biochemical function. Our study thus provides the first link between this protein and the palmoplantar epidermis.

Vyšlo v časopise: A Mutation in the Gene in Dogs with Hereditary Footpad Hyperkeratosis (HFH). PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004370
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004370

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