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: