Dale B A, Kam E
Department of Oral Biology, University of Washington, Seattle.
Arch Dermatol. 1993 Nov;129(11):1471-7. doi: 10.1001/archderm.129.11.1471.
Harlequin ichthyosis is an inherited skin disorder that usually results in death shortly after birth. Although the clinical features of this disorder are well described, the underlying molecular basis is not understood. In this article, we discuss the results of the latest histologic, immunochemical, and Western immunoblotting studies done in our laboratory and propose a hypothesis for molecular basis of this disorder.
Previous experiments done in our laboratory show suggestive evidence for defective lipid synthesis and protein dephosphorylation in harlequin ichthyosis. Our latest study shows that the catalytic subunit of one of the most prevalent protein phosphatase, type 2A protein phosphatase, appears to be altered in some cases of type 2 harlequin ichthyosis.
Based on these observations and the known functions of protein phosphatase in keratinocytes, we hypothesize that the underlying molecular basis of harlequin ichthyosis may be related to mutations affecting protein dephosphorylation. We further describe approaches by which this hypothesis can be tested.
丑角样鱼鳞病是一种遗传性皮肤病，通常会导致患儿在出生后不久死亡。尽管这种疾病的临床特征已有详尽描述，但其潜在的分子基础仍不清楚。在本文中，我们讨论了我们实验室最新进行的组织学、免疫化学和蛋白质免疫印迹研究结果，并提出了关于该疾病分子基础的假说。
我们实验室之前的实验显示了丑角样鱼鳞病中脂质合成缺陷和蛋白质去磷酸化的提示性证据。我们的最新研究表明，在某些2型丑角样鱼鳞病病例中，最常见的蛋白磷酸酶之一，即2A型蛋白磷酸酶的催化亚基似乎发生了改变。
基于这些观察结果以及蛋白磷酸酶在角质形成细胞中的已知功能，我们推测丑角样鱼鳞病的潜在分子基础可能与影响蛋白质去磷酸化的突变有关。我们进一步描述了可以检验这一假说的方法。
