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

被引：195

作者：

Grall, Anais ^{[1
,2
]}

Guaguere, Eric ^{[3
]}

Planchais, Sandrine ^{[1
,2
]}

Grond, Susanne ^{[4
]}

Bourrat, Emmanuelle ^{[5
]}

Hausser, Ingrid ^{[6
,7
]}

Hitte, Christophe ^{[1
,2
]}

Le Gallo, Matthieu ^{[1
,2
]}

Derbois, Celine ^{[8
]}

Kim, Gwang-Jin ^{[9
,10
]}

Lagoutte, Laetitia ^{[1
,2
]}

Degorce-Rubiales, Frederique ^{[11
]}

Radner, Franz P. W. ^{[4
]}

Thomas, Anne ^{[12
]}

Kury, Sebastien ^{[1
,2
,13
]}

Bensignor, Emmanuel ^{[14
]}

Fontaine, Jacques ^{[15
]}

Pin, Didier ^{[16
]}

Zimmermann, Robert ^{[4
]}

Zechner, Rudolf ^{[4
]}

Lathrop, Mark ^{[8
,17
]}

Galibert, Francis ^{[1
,2
]}

Andre, Catherine ^{[1
,2
]}

Fischer, Judith ^{[8
,9
,18
]}

机构：

[1] CNRS, Inst Genet & Dev Rennes, Rennes, France

[2] Univ Rennes 1, Inst Federatif Rech IFR 140, Fac Med, Rennes, France

[3] Clin Vet St Bernard, Lomme Les Lille, France

[4] Karl Franzens Univ Graz, Inst Mol Biosci, Graz, Austria

[5] Hop St Louis, Dept Dermatol, Paris, France

[6] Univ Clin Heidelberg, Dept Dermatol, Heidelberg, Germany

[7] Heidelberg Univ, Electron Microscopy Core Facil, Heidelberg, Germany

[8] Commissariat Energie Atom & Energies Alternat CEA, CNG, Inst Genom, Evry, France

[9] Univ Clin Freiburg, Inst Human Genet, Freiburg, Germany

[10] Univ Freiburg, Fac Biol, D-79106 Freiburg, Germany

[11] Lab Anat Pathol Vet Sud Ouest, Toulouse, France

[12] Antagene, Anim Genet Lab, Limonest, France

[13] Ctr Hosp Univ CHU Nantes, Serv Genet Med, Nantes, France

[14] Clin Vet Boulais, Cesson Sevigne, France

[15] Clin Vet, Brussels, Belgium

[16] VetAgro Sup Campus Vet Lyon, Unite Dermatol, Marcy Letoile, France

[17] CEPH, Fdn Jean Dausset, Paris, France

[18] Univ Freiburg, Zentrum Biosyst Anal, D-79106 Freiburg, Germany

来源：

NATURE GENETICS | 2012年 / 44卷 / 02期

关键词：

LIPID STORAGE DISEASE; TRIGLYCERIDE LIPASE PNPLA2; LAMELLAR ICHTHYOSIS; GENE-MUTATIONS; FAMILY; TRANSGLUTAMINASE; IDENTIFICATION; PATHOGENESIS; HYDROLASE; CGI-58;

D O I：

10.1038/ng.1056

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：140 / 147

页数：8

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