A molecular defect in loricrin, the major component of the cornified cell envelope, underlies Vohwinkel's syndrome
A molecular defect in loricrin, the major component of the cornified cell envelope, underlies Vohwinkel's syndrome
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DOI：
10.1038/ng0596-70
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发表时间：
1996-05-01
期刊：
影响因子：
30.8
通讯作者：
Christiano, AM
中科院分区：
文献类型：
--
作者：
Maestrini, E;Monaco, AP;Christiano, AM
角质形成细胞终末分化涉及多个功能上相互依赖的基因的协调表达，其中许多基因已被定位到染色体 1q21 上的表皮分化复合物 (EDC)。我们已经确定了扩展谱系中 Vohwinkel 综合征与 EDC 区域侧翼标记的关联，最大多点 Lod 得分为 14.3。兜甲蛋白基因的测序揭示了一个插入，该插入改变了 C 端富含 Gly 和 Gln/Lys 结构域的翻译框架，并且可能损害角化。我们的研究结果为人类疾病中 EDC 基因的缺陷提供了第一个证据，并揭示了对角化细胞包膜形成扰动的新见解。
Terminal keratinocyte differentiation involves coordinated expression of several functionally interdependent genes, many of which have been mapped to the epidermal differentiation complex (EDC) on chromosome 1q21. We have identified linkage of Vohwinkel's syndrome in an extended pedigree to markers flanking the EDC region with a maximum multipoint lod score of 14.3. Sequencing of the loricrin gene revealed an insertion that shifts the translation frame of the C-terminal Gly- and Gln/Lys-rich domains, and is likely to impair cornification. Our findings provide the first evidence for a defect in an EDC gene in human disease, and disclose novel insights into perturbations of cornified cell envelope formation.