Department of Molecular Genetics, Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Korytkova 2, SI-1000, Slovenia.
Eur J Dermatol. 2010 May-Jun;20(3):271-5. doi: 10.1684/ejd.2010.0913. Epub 2010 Apr 27.
ATP2A2 encodes the sarco/endoplasmic reticulum Ca2+- ATPase (SERCA2) and has been identified as a defective gene in Darier disease (DD). It is an autosomal dominant genodermatosis, which is characterized by loss of adhesion between suprabasal epidermal keratinocytes (acantholysis) and abnormal keratinization (dyskeratosis). We examined 28 Slovenian patients with DD (the cohort of patients represents over 50% of all DD patients in Slovenia) and screened genomic DNA for ATP2A2 mutations and RNA for splice site mutations. We identified 7 different ATP2A2 mutations, 4 of which are novel: A516P, R559G, 544+1del6, and 1762-6del18. We also found two previously described polymorphisms 2741+54 G>A in intron XVIII and 2172 G>A (A724A) in exon 15, with allele frequencies of 64.2% and 11.3%, respectively. The mutations are scattered throughout the gene and affect the actuator, phosphorylation, stalk and transmembrane domains of SERCA2. A P160L mutation in a Slovene patient with severe DD and a history of deafness is another consistent genotype-phenotype correlation. It seems that mutations of the ATP2A2 gene may also play a role in the pathogenesis of deafness, which seems to be a new phenotypic characteristic of DD patients.
ATP2A2 编码肌浆/内质网 Ca2+-ATP 酶 (SERCA2)，已被确定为 Darier 病 (DD) 的缺陷基因。它是一种常染色体显性遗传皮肤病，其特征是上皮角质形成细胞（棘层松解）之间的附着力丧失和异常角化（角化不良）。我们检查了 28 名斯洛文尼亚 DD 患者（该患者队列代表了斯洛文尼亚所有 DD 患者的 50%以上），并筛选了 ATP2A2 基因突变的基因组 DNA 和剪接位点突变的 RNA。我们确定了 7 种不同的 ATP2A2 突变，其中 4 种是新的：A516P、R559G、544+1del6 和 1762-6del18。我们还发现了两个先前描述的多态性：内含子 XVIII 中的 2741+54 G>A 和外显子 15 中的 2172 G>A (A724A)，等位基因频率分别为 64.2%和 11.3%。突变散布在整个基因中，影响 SERCA2 的执行器、磷酸化、茎和跨膜结构域。一名斯洛文尼亚严重 DD 患者和耳聋病史的 P160L 突变是另一个一致的基因型-表型相关性。似乎 ATP2A2 基因突变也可能在耳聋发病机制中发挥作用，这似乎是 DD 患者的一个新的表型特征。
