Loss of Corneodesmosin Leads to Severe Skin Barrier Defect, Pruritus, and Atopy: Unraveling the Peeling Skin Disease
Loss of Corneodesmosin Leads to Severe Skin Barrier Defect, Pruritus, and Atopy: Unraveling the Peeling Skin Disease
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DOI：
10.1016/j.ajhg.2010.07.005
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发表时间：
2010-08-13
影响因子：
9.8
通讯作者：
Hennies, Hans Christian
中科院分区：
文献类型：
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作者：
Oji, Vinzenz;Eckl, Katja-Martina;Hennies, Hans Christian
全身性脱皮皮肤病是一种常染色体隐性鱼鳞样红皮病，其特征是皮肤的终身斑片状脱皮。经过全基因组连锁分析，我们在一个具有全身性皮肤脱皮、瘙痒和食物过敏的大近亲家族中发现了CDSN纯合无义突变，导致角膜粘连蛋白完全丧失。单纯性毛少症可能与特异性显性CDSN突变相关，与之相反，脱皮皮肤病的特征是CDSN表达完全缺失。皮肤表型与最近的小鼠Cdsn敲除模型一致。使用三维人体皮肤模型，我们证明缺乏角膜粘连蛋白会导致表皮屏障缺陷，这可能是导致特应性疾病的易感性的原因，并且我们证实了角膜粘连蛋白作为表皮粘附分子的决定性作用。因此，脱皮病将代表一种新的模式疾病的特应性疾病，类似于内瑟顿综合征和寻常性鱼鳞病在最近的过去。
Generalized peeling skin disease is an autosomal-recessive ichthyosiform erythroderma characterized by lifelong patchy peeling of the skin. After genome-wide linkage analysis, we have identified a homozygous nonsense mutation in CDSN in a large consanguineous family with generalized peeling skin, pruritus, and food allergies, which leads to a complete loss of corneodesmosin. In contrast to hypotrichosis simplex, which can be associated with specific dominant CDSN mutations, peeling skin disease is characterized by a complete loss of CDSN expression. The skin phenotype is consistent with a recent murine Cdsn knockout model. Using three-dimensional human skin models, we demonstrate that lack of corneodesmosin causes an epidermal barrier defect supposed to account for the predisposition to atopic diseases, and we confirm the role of corneodesmosin as a decisive epidermal adhesion molecule. Therefore, peeling skin disease will represent a new model disorder for atopic diseases, similarly to Netherton syndrome and ichthyosis vulgaris in the recent past.