Grall A, Guaguère E, Planchais S, et al. PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans. Nature Genetics 2012, ePub. Abstract.
PubMed ID (PMID): 22246504
Reprint: C. André
Comments: This is an elegant and rigorous study that combines different genetic and molecular techniques to unravel the etiopathogenesis of ichthyosis of golden retrievers. Firstly, in a genetic association study using only 40 golden retriever dogs, the authors identify a single locus in chromosome 12 that shows highly significant association with the hereditary non-epidermolytic retention ichthyosis described in 2007 in this breed. Furthermore, a causal mutation is identified in PNPLA1 (patatin-like phospholipase domain-containing protein 1), which consists of an indel (insertion-deletion) in exon 8 leading to a premature stop codon. This mutation constitutes a completely new molecular mechanism causing ichthyosis and which involves epidermal lipid metabolism. Finally, the authors also identify two mutations in the PNPLA1 gene in six humans affected by a variant of autosomal recessive congenital ichthyosis (ARCI). Therefore, this paper confirms the validity of using dogs as an unique model to pinpoint phenotype-genotype correlations and to identify new mutations leading to human diseases.
Recommended by: Lluís Ferrer, University of Barcelona, Catalonia, Spain
