Background Erythrokeratodermia variabilis et progressiva (EKVP, OMIM 133200) is a rare hereditary disorder characterized by varies from transient, fast moving erythema to persistent brown hyperkeratotic plaques. Recently, mutations in the genes gap junction alpha 1 gene (GJA1), GJB3, and GJB4 have been reported to cause EKVP. Here, we report the identification of two de novo missense mutations in the GJA1 gene in two unrelated individuals with EKVP. Methods The patients and his family members were subjected to mutation detection in the candidate gene GJA1, GJB3, and GJB4 by Sanger sequencing. The expression of connexin (Cx) 43 was detected by immunohistochemistry and immunofluorescence (IF) studies in the lesions. Results A 12‐year‐old boy presented with multiple hyperkeratotic plaques on the face, neck, elbows, wrists, limbs, knees, inguinal region, hands, and feet. A 7‐year‐old girl presented with symmetrical erythematous, plaques on the hands, feet, wrists, and ankles. A novel heterozygous missense mutation c.848C > T (p.P283L) in exon 2 of the GJA1 gene was identified in both patients. A novel heterozygous missense mutation c.869C > A (p.T290N) in exon 2 of the GJA1 gene was also identified in the boy. These mutations were not found in the unaffected family members and 100 normal controls. In the patients’ lesions, Cx43 protein was located to the cytomembrane and cytoplasm in the stratum corneum, and granular layer. Compound heterozygous mutations in the boy showed a more severe clinical phenotype and cytoplasmic mislocalization. Conclusions The novel mutations c.848C > T (p.P283L) and c.869C > A(p.T290N) arose de novo and were considered as the cause of two Chinese EKVP. GJA1 P283L and T290N mutations lead to Cx43 protein cytoplasmic mislocalization. Our finding expands the mutant spectrum of GJA1 gene and adds new understanding of the genotype‐phenotype correlation.

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Summary Fonsecaea monophora is a member of dematiaceous fungi capable of causing chromoblastomycosis through traumatic injury. However, little is known about the pathogenesis and early interactions between F. monophora and host. The aim of this study was to explore the potential mechanism of macrophages against F. monophora, especially the role of melanin during the pathogenic process. We carried out RNA sequencing based on the Illumina system. It showed that according to melanin contents, different strains of F. monophora induced different transcriptional profilings in macrophages. Functional analyses suggested the biological functions of differentially expressed genes were closely related to immune response, and the melanin might affect the interactions by regulating the MAPK signalling pathway of macrophages. Our results provide insights into the pathogenesis of infection by F. monophora conidia.