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

Anaïs Grall; 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 Radner; Anne Thomas; Sébastien Küry; Emmanuel Bensignor; Jacques Fontaine; Didier Pin; Robert Zimmermann; Rudolf Zechner; Mark Lathrop; Francis Galibert; Catherine André; Judith Fischer

doi:10.1038/ng.1056

Journal articles

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

Anaïs Grall ¹ Eric Guaguère ² Sandrine Planchais ¹ Susanne Grond ³ Emmanuelle Bourrat ⁴ Ingrid Hausser ^{5, 6} Christophe Hitte ¹ Matthieu Le Gallo ¹ Céline Derbois ^{7, 8} Gwang-Jin Kim ^{9, 10} Laëtitia Lagoutte ¹ Frédérique Degorce-Rubiales ¹¹ Franz Radner ³ Anne Thomas ¹² Sébastien Küry ^{1, 13} Emmanuel Bensignor ¹⁴ Jacques Fontaine ¹⁵ Didier Pin ¹⁶ Robert Zimmermann ³ Rudolf Zechner ³ Mark Lathrop ^{7, 8, 17} Francis Galibert ¹ Catherine André ^{1, *} Judith Fischer ^{7, 8, 9, 18}

* Corresponding author

1 IGDR - Institut de Génétique et Développement de Rennes

2 Clinique Vétérinaire Saint Bernard

3 Institute of Molecular Biosciences

4 Service de dermatologie [Paris]

5 Department of dermatology

6 Electron Microscopy Core Facility

7 CNG - Centre National de Génotypage

8 IG - Institut de Génomique d'Evry

9 Institute for Human Genetics

10 Faculty for Biology

11 Laboratoire d'Anatomie Pathologique Vétérinaire du Sud-Ouest

12 Animal Genetics Laboratory

13 Service d'ORL et de Chirurgie Cervicofaciale

14 Clinique Vétérinaire de la Boulais

15 Clinique vétérinaire

16 ICE - Interactions Cellules Environnement - UR

17 CEPH - Centre d'Etude du Polymorphisme Humain

18 Zentrum für Biosystemanalyse

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.

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Genetics

Life Sciences [q-bio] / Human health and pathology / Dermatology

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https://www.hal.inserm.fr/inserm-00662852
Contributor : Hervé de Villemeur <>
Submitted on : Wednesday, January 25, 2012 - 12:49:45 PM
Last modification on : Thursday, January 14, 2021 - 11:16:02 AM

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

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

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