2. Academic Validation
  3. PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans

PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans

  • Nat Genet. 2012 Jan 15;44(2):140-7. doi: 10.1038/ng.1056.
Anaïs Grall 1,  Eric Guaguère,  Sandrine Planchais,  Susanne Grond,  Emmanuelle Bourrat,  Ingrid Hausser,  Christophe Hitte,  Matthieu Le Gallo,  Céline Derbois,  Gwang-Jin Kim,  Laëtitia Lagoutte,  Frédérique Degorce-Rubiales,  Franz P W Radner,  Anne Thomas,  Sébastien Küry,  Emmanuel Bensignor,  Jacques Fontaine,  Didier Pin,  Robert Zimmermann,  Rudolf Zechner,  Mark Lathrop,  Francis Galibert,  Catherine André,  Judith Fischer
Affiliations

Affiliation

  • 1 Centre National de la Recherche Scientifique, Institut de Génétique et Développement de Rennes, Rennes, France.
PMID: 22246504 DOI: 10.1038/ng.1056
Abstract

Ichthyoses comprise a heterogeneous group of genodermatoses characterized by abnormal desquamation over the whole body, for which the genetic causes of several human forms remain unknown. We used a spontaneous dog model in the golden retriever breed, which is affected by a lamellar ichthyosis resembling human autosomal recessive congenital ichthyoses (ARCI), to carry out a genome-wide association study. We identified a homozygous insertion-deletion (indel) mutation in PNPLA1 that leads to a premature stop codon in all affected golden retriever dogs. We subsequently found one missense and one nonsense mutation in the catalytic domain of human PNPLA1 in six individuals with ARCI from two families. Further experiments highlighted the importance of PNPLA1 in the formation of the epidermal lipid barrier. This study identifies a new gene involved in human ichthyoses and provides insights into the localization and function of this yet uncharacterized member of the PNPLA protein family.

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