Tuesday, January 24, 2012

Novel Gene Mutation Causes Autosomal Recessive Congenital Ichthyosis of Golden Retrievers and Humans

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
ReprintC. 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