A possible role for second‐hit postzygotic GJB2 mutation in porokeratotic eccrine ostial and dermal duct nevus

Abstract

Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) is a rare type of epidermal nevus involving the eccrine acrosyringia. It typically presents as asymptomatic linear keratotic papules and plaques along the lines of Blaschko and predominantly affects the extremities. This disease has recently been linked to somatic mutations within the GJB2 locus. Only four GJB2 mutations have been previously documented for PEODDN, and the underlying genetic basis remains inconclusive. Herein, we report an 18‐year‐old female with a hyperkeratotic plaque on the dorsa of the proximal interphalangeal joint of her right ring finger, as well as multiple small hyperkeratotic papules linearly distributed on the lateral sides of her fingers occurring since birth. Histopathological results revealed prominent parakeratotic cornoid lamella‐like tiers at the opening of the eccrine secretory ducts. Whole‐exome sequencing of the affected skin tissue revealed a heterozygous germline mutation and a postzygotic somatic mutation in GJB2. In summary, this study presents a case of PEODDN with compound heterozygous mutations in GJB2, which broadens the genetic spectrum of this disease entity and implies a possible role for second‐hit mutations in the pathogenesis of PEODDN.

Mosaic GJB2 mutations in widespread porokeratotic adnexal ostial nevus: Report of two patients

“…Germline GJB2 mutations have been linked to cutaneous disorders, such as keratitis‐ichthyosis‐deafness (KID) syndrome (OMIM 148210) and hystrix‐like ichthyosis with deafness syndrome (OMIM 602540) 4 . PEODDN has been related to somatic GJB2 mutations in epidermis, supported by four reports, representing five cases with limited unilateral and linear keratotic lesions 3,5–7 . Three of these patients harbored somatic heterozygous GJB2 mutations detected in skin lesions but not in blood.…”

“…4 PEODDN has been related to somatic GJB2 mutations in epidermis, supported by four reports, representing five cases with limited unilateral and linear keratotic lesions. 3,[5][6][7] Three of these patients harbored somatic heterozygous GJB2 mutations detected in skin lesions but not in blood. Second-hit mutations of GJB2 were detected in the other two patients' lesional epidermis.…”