近日,《自然—遗传学》(Nature Genetics)上发表的一项研究成功称,共有的遗传基础可导致人类患上一种存在于黄金猎犬身上的罕见皮肤病。
这种皮肤病我们称之为先天性鱼鳞病,患有此病的人在出生后不久,全身皮肤会呈现鱼鳞状。Catherine André, Judith Fischer与其他研究人员通过研究犬类独特的繁殖历史,从患有该病的黄金猎犬身上鉴别出了致病基因,并将其命名为PNPLA1。通过进一步分析PNPLA1,研究人员发现,患有类似皮肤病的人身上同样存在该基因,并且在每两个家族中,就有六个人携带有这种基因的两种分裂类型。
PNPLA1基因通过皮肤表皮层表达,对维持皮肤的屏障功能具有重要影响。其所属的蛋白家族可改变类脂结构,包括形成细胞外膜的类脂种类。(生物谷 Bioon.com)
doi:10.1038/ng.1056
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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 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
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.