Erythrokeratodermia variabilis et progressiva (EKVP) is a rare hereditary skin disorder characterized by hyperkeratotic plaques and erythematous patches that progressively worsen with age. This disorder has been associated with variants in three connexin encoding genes (GJA1, GJB3, GJB4) and four unrelated genes (KRT83, KDSR, TRPM4, PERP). Most cases of connexin-linked EKVP exhibit an autosomal dominant mode of inheritance, with rare autosomal recessive cases. Collectively, evidence suggests that connexin variants associated with EKVP elicit a plethora of molecular defects including impaired gap junction (GJ) formation, dysregulated hemichannel and/or GJ channel function, cytotoxicity, dominant disruption of co-expressed connexins, and/or altered turnover kinetics. Here, we review the progress made in understanding the genetic and molecular basis of EKVP associated with connexin gene variants. We also discuss the landscape of treatment options used for this disorder and the future directions for research into this rare condition.

中文翻译：

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连接蛋白相关皮肤病的遗传和分子基础。


静脉曲张红肿和进行性红膜皮肤病 （EKVP） 是一种罕见的遗传性皮肤病，其特征是角化过度斑块和红斑斑块，随着年龄的增长而逐渐恶化。这种疾病与三个连接蛋白编码基因 （GJA1、GJB3、GJB4） 和四个不相关基因 （KRT83、KDSR、TRPM4、PERP） 的变异有关。大多数连接蛋白连接的 EKVP 病例表现出常染色体显性遗传模式，罕见的常染色体隐性遗传病例。总的来说，证据表明，与 EKVP 相关的连接蛋白变体会引发大量的分子缺陷，包括间隙连接 （GJ） 形成受损、半通道和/或 GJ 通道功能失调、细胞毒性、共表达连接蛋白的显性破坏和/或周转动力学改变。在这里，我们回顾了在理解与连接蛋白基因变异相关的 EKVP 的遗传和分子基础方面取得的进展。我们还讨论了用于这种疾病的治疗方案的前景以及这种罕见病症研究的未来方向。