A Somatic p.G45E GJB2 Mutation Causing Porokeratotic Eccrine Ostial and Dermal Duct Nevus.

IMPORTANCE: Recent data demonstrated somatic mutations in GJB2 that were present in affected porokeratotic eccrine ostial and dermal duct nevus (PEODDN) tissue but absent in unaffected skin. Recognizing that PEODDN lesions can also appear in individuals with keratitis-ichthyosis-deafness syndrome and finding somatic mutations in their cohort, the authors concluded that somatic GJB2 mutation may cause PEODDN. By using whole-exome sequencing, we show that somatic GJB2 mutation alone is sufficient to cause PEODDN. OBSERVATIONS: We performed whole-exome sequencing of paired blood and affected tissue samples isolated from a PEODDN lesion of a primary school-aged female patient with bands of hyperkeratotic-affected skin on the upper and lower extremities and trunk, and identified a single, protein-damaging p.Gly45Glu GJB2 mutation present in tissue samples but not in blood samples. CONCLUSION AND RELEVANCE: Our results prove that somatic GJB2 mutation is sufficient to cause PEODDN. Dominantly inherited GJB2 mutations, including the p.Gly45Glu found in our case, have been shown to cause the severe multisystem disorder keratitis-ichthyosis-deafness syndrome. GJB2 encodes connexin 26, a gap junction protein, which permits intercellular ion and macromolecule flux. Individuals with somatic mosaicism are at risk for transmitting systemic disease to their offspring, and all individuals with PEODDN lesions should be counseled regarding the risk of having a child with keratitis-ichthyosis-deafness syndrome.