OMIA 001588-9615 : Ichthyosis, PNPLA1-related in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 612121

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2012

Cross-species summary: Called Autosomal Recessive Congenital Ichthyosis (ARCI) in humans

Species-specific name: This entry was previously called Ichthyosis, Golden Retriever

Species-specific description: At the time when the causal mutation for this disorder was discovered to be in the PNPLA1 gene in Golden Retrievers, this gene had not been implicated in any human cases of the same disorder nor in any other diseases. Having made the canine discovery, Grall et al. (2012) then sequenced the PNPLA1 gene in human families with affected individuals, and discovered "one missense and one nonsense mutation in the catalytic domain of human PNPLA1 in six individuals with ARCI from two families". This is an original way to discover clinically-important human mutations: to start by identifying what appear to be homologous disorders in spontaneous animal models, to identify the causal mutation in the animal model, and then use such knowledge to inform human medicine and also benefit veterinary medicine.

(Thanks to Catherine André and Judith Fischer for their suggestions to FN in relation to this and other sections of this page; 27 January 2012)

Mapping: Unlike ichthyosis in the Jack Russell terrier (OMIA 000546-9615) which maps to canine chromosome CFA8 (TGM1 gene), and ichthyosis in the Norfolk terrier (OMIA 001415-9615) which maps to canine chromosome CFA9 (KRT10 gene), ichthyosis in Golden Retrievers maps to a locus on CFA12 (PNPLA1 gene), as shown by Grall et al. (2012), who conducted a GWAS on 20 affecteds and 20 controls, each genotyped with the Affymetrix v2 canine SNP.

Molecular basis: The Golden Retriever causal mutation was reported by Grall et al. (2012) to be an "insertion-deletion (indel) mutation in PNPLA1 that leads to a premature stop codon in all affected golden retriever dogs". Using the genetic variant nomeclature as of 2015, the causative variant can be described as c.1445_1447delinsTACTACTA or p.N482Ifs*11.

Genetic testing: A genetic test has been licenced to Antagene, Lyon, France (www.antagene.com).

Breed: Golden Retriever.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
PNPLA1 patatin-like phospholipase domain containing 1 Canis lupus familiaris 12 NC_006594.3 (5377430..5423556) PNPLA1 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective.

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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
Golden Retriever Ichthyosis, PNPLA1-related PNPLA1 indel, small (<=20) c.1445_1447delinsTACTACTA p.N482Ifs*11 2012 22246504

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2016 Leroy, G., Besbes, B., Boettcher, P., Hoffmann, I., Capitan, A., Baumung, R. :
Rare phenotypes in domestic animals: unique resources for multiple applications. Anim Genet 47:141-53, 2016. Pubmed reference: 26662214. DOI: 10.1111/age.12393.
Tamamoto-Mochizuki, C., Banovic, F., Bizikova, P., Laprais, A., Linder, K.E., Olivry, T. :
Autosomal recessive congenital ichthyosis due to PNPLA1 mutation in a golden retriever-poodle cross-bred dog and the effect of topical therapy. Vet Dermatol 27:306-e75, 2016. Pubmed reference: 27237723. DOI: 10.1111/vde.12323.
2012 Grall, A., Guaguère, E., Planchais, S., Grond, S., Bourrat, E., Hausser, I., Hitte, C., Le Gallo, M., Derbois, C., Kim, G.J., Lagoutte, L., Degorce-Rubiales, F., Radner, F.P., Thomas, A., Küry, S., Bensignor, E., Fontaine, J., Pin, D., Zimmermann, R., Zechner, R., Lathrop, M., Galibert, F., André, C., Fischer, J. :
PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans. Nat Genet 44:140-7, 2012. Pubmed reference: 22246504. DOI: 10.1038/ng.1056.
2011 Owczarek-Lipska, M., Thomas, A., André, C., Hölzer, S., Leeb, T. :
[Frequency of gene defects in selected European retriever populations]. Schweiz Arch Tierheilkd 153:418-20, 2011. Pubmed reference: 21866517. DOI: 10.1024/0036-7281/a000236.
2009 Guaguere, E., Bensignor, E., Küry, S., Degorce-Rubiales, F., Muller, A., Herbin, L., Fontaine, J., André, C. :
Clinical, histopathological and genetic data of ichthyosis in the golden retriever: a prospective study. J Small Anim Pract 50:227-35, 2009. Pubmed reference: 19413748. DOI: 10.1111/j.1748-5827.2009.00730.x.
2008 Cadiergues, M.C., Patel, A., Shearer, D.H., Fermor, R., Miah, S., Hendricks, A. :
Cornification defect in the golden retriever: clinical, histopathological, ultrastructural and genetic characterisation. Vet Dermatol 19:120-9, 2008. Pubmed reference: 18477327. DOI: 10.1111/j.1365-3164.2008.00667.x.
Mauldin, E.A., Credille, K.M., Dunstan, R.W., Casal, M.L. :
The clinical and morphologic features of nonepidermolytic ichthyosis in the golden retriever. Vet Pathol 45:174-80, 2008. Pubmed reference: 18424829. DOI: 10.1354/vp.45-2-174.
2007 Guaguere, E., Bensignor, E., Muller, A., Degorce-Rubiales, F., Andre, C. :
Epidemiological, clinical, histopathological and ultrastructural aspects of ichthyosis in golden retrievers: a report of 50 cases. Veterinary Dermatology 18:382-383, 2007.
2004 Hall, J.A., Yager, J. :
Diagnostic dermatology. Can Vet J 45:872, 874, 2004. Pubmed reference: 15532893.

Edit History


  • Created by Frank Nicholas on 21 Jul 2011
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Frank Nicholas on 26 Jan 2012
  • Changed by Frank Nicholas on 27 Jan 2012
  • Changed by Frank Nicholas on 29 Jan 2012
  • Changed by Frank Nicholas on 20 May 2013
  • Changed by Tosso Leeb on 23 Dec 2015
  • Changed by Frank Nicholas on 23 Mar 2017