November 30, 2025

A novel missense mutation responsible for a unique erythrokeratodermia variabilis patient with skin lesions in a swirling pattern

SHSheng Yuan Hua BFBiqing Fang YLYazun Liu

Key Points

Skin lesions presented in a swirling pattern were observed in the male infant with erythrokeratodermia variabilis.
Whole exome sequencing identified a novel missense mutation in the GJB3 gene, expanding the genetic basis of EKV.
Observational analysis highlighted that the unique mutation may affect the phenotypic spectrum associated with the disorder.
Findings underscore the importance of genetic screening in understanding rare skin diseases like EKV.

Abstract

Abstract Erythrokeratodermia variabilis (EKV) is a rare, inherited skin disease characterized by migratory erythematous areas and fixed hyperkeratosis plaques, which is most commonly caused by mutations in the GJB3, GJB4 or GJA1 gene. This study reports a 5-month-old male infant presenting with erythematous skin lesions on the trunk and brown hyperkeratotic plaques with a unique swirling pattern on the extremities. Whole exome sequencing (WES) revealed a heterozygous missense mutation c.134GC in the GJB3 gene, which has not been reported before. The PROVEAN analysis revealed a PROVEAN score of -3.065, which was below the threshold of -2.5, moreover, the 3-D structure predicted missense mutation p.Gly45Ala could compromise the three-dimensional stability of the GJB3 protein, suggesting a deleterious effect. In Conclusion, we report a novel missense mutation (p. Gly45Ala) in the GJB3 gene that caused EKV accompanying with a unique swirling pattern in a Chinese family, which broadens the genetic and phenotypic spectrum of EKV.

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