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

Erythrokeratodermia variabilis et progressiva (EKVP) is a rare, inherited skin disease characterized by migratory erythematous areas and fixed hyperkeratosis plaques, which is most commonly caused by mutations in GJB3, GJB4 or GJA1. A 5-month-old male infant presented with erythematous skin lesions on the trunk and brown hyperkeratotic plaques, with a unique swirling pattern on the extremities. Whole-exome sequencing revealed a heterozygous missense mutation c.134G>C in GJB3, which has not previously been reported. PROVEAN (Protein Variation Effect Analyser) analysis revealed a score of -3.065, which was below the threshold of -2.5. In addition, the three-dimensional (3D) structure predicted that missense mutation p.Gly45Ala could compromise the 3D stability of the GJB3 protein, suggesting a deleterious effect. This novel missense mutation in GJB3 that caused EKVP with a unique swirling pattern in a Chinese family broadens the genetic and phenotypic spectrum of EKVP.