鱼鳞病是由遗传决定的表皮角质化疾病,其特征是存在不同程度的鳞屑,角化过度,和红皮病通常与掌足底角化病有关。已经提出了对这些疾病的不同分类,通常基于涉及的基因和/或临床表现。这些疾病的临床特征在不同的遗传实体中表现出一些表型重叠。主要取决于突变的外显率。在这项研究中,使用临床,遗传,和分子方法,我们分析了一个有两个受影响成员的家庭,他们的临床和组织学特征类似于变异型红皮角化症(EKV)或一种红皮过度角化症伴掌plant角化症。尽管有临床表现,我们证明了受影响的患者在ABCA12基因中的两个不同突变是遗传双杂合子,已知与丑角鱼鳞病有关。为了解释我们患者的轻度表型,我们对皮肤进行了分子表征。在表皮的上层,结果表明,葡萄糖基神经酰胺(GlcCer)的片状存在,它是ABCA12转运的脂质,对皮肤不通透性有重要作用。的确,检测到的两个突变并没有完全消除ABCA12活性,表明轻度表型是由于酶功能的部分丧失,从而产生类似EKVP的中间表型,由于GlcCer沉积物的部分消耗。
Ichthyoses are genetically determined cornification disorders of the epidermis characterized by the presence of different degrees of scaling,
hyperkeratosis, and erythroderma often associated with palmoplantar keratoderma. Different classifications of these diseases have been proposed, often based upon the involved genes and/or the clinical presentation. The clinical features of these diseases present some overlap of phenotypes among distinct genetic entities, depending mainly on the penetrance of mutations. In this study, using a clinical, genetic, and molecular approach, we analyzed a family with two affected members who had clinical and histological features resembling erythrokeratodermia variabilis (EKV) or a type of erythrodermic
hyperkeratosis with palmoplantar keratoderma. Despite of the clinical presentation, we demonstrated that the affected patients were genetically double heterozygous for two different mutations in the ABCA12 gene, known to be responsible for harlequin ichthyosis. To explain the mild phenotype of our patients, we performed a molecular characterization of the skin. In the upper layers of the epidermis, the results showed a patchy presence of the glucosyl-ceramides (GlcCer), which is the lipid transported by ABCA12, fundamental in contributing to skin impermeability. Indeed, the two mutations detected do not completely abolish ABCA12 activity, indicating that the mild phenotype is due to a partial loss of function of the enzyme, thus giving rise to an intermediate phenotype resembling EKVP, due to a partial depletion of GlcCer deposition.