Jia Zhang ^1* Shengyuan Hua ² Yun Yang ² Qiufang Qian ² Xue Zheng ^3*

• ¹ Department of Dermatology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
• ² Shanghai Children's Hospital, Shanghai, Shanghai Municipality, China
• ³ Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai, China

Background: 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.Objective: To determine the definitive diagnosis of a 5-month-old male infant with erythematous skin lesions on the trunk and brown hyperkeratosis plaque that occurred with a swirling pattern on the extremities.Methods:Whole exome sequencing (WES) and Sanger sequencing were performed to make a definite dignosis.The PyMOL software (www.pymol.org/) was used to draw the structural models.The PROVEAN analysis software was utilized to assess the functional changes in the proteins resulting from the novel missense mutation.Results: Mutation analysis revealed a heterozygous missense mutation c.134G>C in the GJB3 gene ,which has not been reported in the literature.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.We reported 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.