Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease
Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease
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DOI：
10.1038/6784
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发表时间：
1999-03-01
期刊：
影响因子：
30.8
通讯作者：
Hovnanian, A
中科院分区：
文献类型：
--
作者：
Sakuntabhai, A;Ruiz-Perez, V;Hovnanian, A
Darier病（DD）是一种常染色体显性遗传的皮肤病，其特征是表皮细胞之间的粘附丧失（棘层松解）和异常角化。最近，我们构建了一个2.4 Mb、Pi衍生的人工染色体重叠群，涵盖染色体12 q23 -24.1上的DD候选区域。在筛选了定位于该区域的几个基因后，我们确定了ATP 2A 2基因的突变，该基因编码肌浆网/内质网Ca 2 +-ATP酶2型同种型（SERCA 2），并在角质形成细胞中高度表达。共发现13个突变，包括移码缺失。框内缺失或插入、剪接位点突变和功能结构域中的非保守错义突变。我们的研究结果表明，ATP 2A 2的突变导致DD，并揭示了该泵在调节细胞间粘附和表皮分化的Ca 2+信号通路中的作用。
Darier disease (DD) is an autosomal-dominant skin disorder characterized by loss of adhesion between epidermal cells (acantholysis) and abnormal keratinization. Recently we constructed a 2.4-Mb, Pi-derived artificial chromosome contig spanning the DD candidate region on chromosome 12q23-24.1. After screening several genes that mapped to this region, we identified mutations in the ATP2A2 gene, which encodes the sarco/endoplasmic reticulum Ca2+-ATPase type 2 isoform (SERCA2) and is highly expressed in keratinocytes. Thirteen mutations were identified, including frameshift deletions. in-frame deletions or insertions, splice-site mutations and non-conservative missense mutations in functional domains. Our results demonstrate that mutations in ATP2A2 cause DD and disclose a role for this pump in a Ca2+-signalling pathway regulating cell-to-cell adhesion and differentiation of the epidermis.