OMIA 001864-9615 : Ectodermal dysplasia/skin fragility syndrome in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 604536

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2012

Species-specific symbol: ED-SFS

History: The first report of this disorder in animals was in Chesapeake Bay retriever dogs, by Olivry et al. (2012).

Inheritance: The results of a pedigree analysis conducted by Olivry et al. (2012) were "most consistent with an autosomal recessive mode of inheritance".

Molecular basis: Extensive and detailed clinical, histological, electron micrographical and protein immunomapping investigations (the latter showing a lack of plakophilin-1 (PKP1) in affected dogs) by Olivry et al. (2012) suggested a strong candidate gene. Sequencing of the exons and exon-intron junctions of the canine PKP1 gene revealed a causative mutation: "a G-to-C conversion at the IVS1 splice donor site of the first intron . . . , which was homozygous in affected puppies and heterozygous in their parents available for testing. This conversion results in a destruction of the intronic splice donor site resulting in a continual read through to a premature stop codon located nine codons downstream from the mutation . . . . As a consequence, the mutated protein is predicted to be truncated and composed of 75 instead of 749 aminoacids." Using the genetic variant nomenclature of 2015, the causative variant can be decribed as c.202+1G>C. (thanks to Hamutal Mazrier for alerting FN to this discovery)

Clinical features: As reported by Olivry et al. (2012), "In all affected dogs, clinical signs occurred immediately after birth with spontaneous sloughing of the nose and footpad epithelium and bleeding of the ear tips if traumatized. Within 48 hours of birth, the lips and facial superficial skin layers also sloughed when rubbed dry or licked by the mother. Three dogs were kept alive by their breeder for three months; all exhibited waxing and waning superficial skin sloughing with erosions and fissures at areas of friction (axillae, groin, caudal tarsi, footpads), concave ear pinnae and mucocutaneous junctions (nasal planum, philtrum, lips, periocular area)".

Prevalence: This variant has also been detected during routine genetic testing, in Golden Retrievers (Frank Coopman, pers. comm., 2017)

Breeds: Chesapeake Bay Retriever, Golden Retriever.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
PKP1 plakophilin 1 (ectodermal dysplasia/skin fragility syndrome) Canis lupus familiaris 7 NC_006589.3 (1966910..1921143) PKP1 Homologene, Ensembl, NCBI gene

Variants

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Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Chesapeake Bay Retriever Golden Retriever Ectodermal dysplasia/skin fragility syndrome PKP1 splicing CanFam3.1 7 g.1966531G>C c.202+1G>C 2012 22384142 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

Reference


2012 Olivry, T., Linder, K.E., Wang, P., Bizikova, P., Bernstein, J.A., Dunston, S.M., Paps, J.S., Casal, M.L. :
Deficient plakophilin-1 expression due to a mutation in PKP1 causes ectodermal dysplasia-skin fragility syndrome in Chesapeake Bay retriever dogs. PLoS One 7:e32072, 2012. Pubmed reference: 22384142. DOI: 10.1371/journal.pone.0032072.

Edit History


  • Created by Frank Nicholas on 24 Jul 2013
  • Changed by Frank Nicholas on 24 Jul 2013
  • Changed by Frank Nicholas on 25 Jul 2013
  • Changed by Tosso Leeb on 23 Dec 2015
  • Changed by Frank Nicholas on 13 Jul 2017