Foggia Lucie, Hovnanian Alain
Department of Medical Genetics, Pavillon Lefebvre, Purpan Hospital, Place du Dr Baylac, Toulouse cedex 03, France.
Am J Med Genet C Semin Med Genet. 2004 Nov 15;131C(1):20-31. doi: 10.1002/ajmg.c.30031.
The causes of Darier disease (DD) and Hailey-Hailey disease (HHD) have eluded clinicians and scientists for more than 60 years. DD is characterized by loss of adhesion between suprabasal epidermal cells associated with abnormal keratinization, while loss of epidermal cell-to-cell adhesion is predominant in HHD. The genes for both conditions have recently been identified using candidate positional cloning approaches. The gene for DD (ATP2A2) encodes a calcium transport ATPase of the sarco (endo)plasmic reticulum (SERCA2) Verboomen et al. [1992: Biochem J 286(Pt 2):591-595], while the gene for HHD (ATP2C1) codes for a secretory pathway for calcium and manganese transport ATPase of the Golgi apparatus (SPCA1) Hu et al. [2000: Nat Genet 24:61-65]. These results have provided completely new insights into the role of calcium and/or manganese in maintaining skin integrity. Although the precise disease mechanisms remain to be understood, these discoveries open a new field in research for the understanding and the treatment of these distressing disorders.
达里埃病（DD）和黑利-黑利病（HHD）的病因已经困扰临床医生和科学家60多年了。DD的特征是基底上层表皮细胞之间的黏附丧失并伴有异常角化，而在HHD中表皮细胞间黏附丧失则占主导地位。最近通过候选定位克隆方法确定了这两种疾病的相关基因。DD的相关基因（ATP2A2）编码一种肌质（内质）网钙转运ATP酶（SERCA2）（韦尔布门等人，1992年：《生物化学杂志》286卷第2期：591 - 595页），而HHD的相关基因（ATP2C1）编码一种高尔基体钙和锰转运ATP酶分泌途径（SPCA1）（胡等人，2000年：《自然遗传学》24卷：61 - 65页）。这些结果为钙和/或锰在维持皮肤完整性中的作用提供了全新的见解。尽管确切的疾病机制仍有待了解，但这些发现为研究这些令人苦恼的疾病的理解和治疗开辟了一个新领域。
