Department of Dermatology, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.
Institute of Psoriasis, School of Medicine, Tongji University, Shanghai, China.
Exp Dermatol. 2022 Apr;31(4):594-599. doi: 10.1111/exd.14490. Epub 2021 Nov 7.
Erythrokeratodermia variabilis et progressiva (EKVP) is a rare genodermatosis of clinical and genetic heterogeneity, characterized by the manifestations of localized or disseminated persistent hyperkeratotic plagues and stationary to migratory transient erythematous patches. The majority of EKVP cases display an autosomal dominant mode of inheritance with incomplete penetrance, although recessive transmission has also been described. Mutations associated with EKVP have been primarily detected in connexin (Cx) genes. We herein reported a Chinese sporadic case of late-onset EKVP with a novel heterozygous missense mutation c.109G>A (p.V37M) in GJB4 (Cx30.3) gene, which resulted in a significant reduction of GJB4 expression in the epidermis of the patient. In accordance, while wild-type GJB4 localized at the cell membrane of HeLa cells forming intercellular junctions and intracellular puncta, V37M mutant variant was diffusely expressed within HeLa cells at a considerably lower level. Our findings reveal an essential role of GJB4 in the pathogenesis of EKVP and provides insights into the therapeutic potential of the disease.
进行性全身性红斑角化症（EKVP）是一种罕见的临床和遗传异质性的皮肤遗传病，其特征为局灶性或播散性持续性角化过度斑块和静止性至迁移性暂时性红斑斑块。大多数 EKVP 病例表现为不完全外显的常染色体显性遗传模式，尽管也描述了隐性遗传。与 EKVP 相关的突变主要在连接蛋白（Cx）基因中检测到。本文报道了一例中国散发的迟发性 EKVP 病例，其 GJB4（Cx30.3）基因存在杂合错义突变 c.109G>A（p.V37M），导致患者表皮中 GJB4 表达显著减少。相应地，野生型 GJB4 定位于形成细胞间连接和细胞内斑点的 HeLa 细胞的细胞膜上，而 V37M 突变变体在 HeLa 细胞内以相当低的水平弥散表达。我们的研究结果揭示了 GJB4 在 EKVP 发病机制中的重要作用，并为该疾病的治疗潜力提供了新的见解。
