33701 Porokeratotic eccrine ostial and dermal duct nevus caused by a second-hit postzygotic GJB2 mutation

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 which predominantly affects the extremities, and the disease has recently been linked to GJB2 somatic mutations. To the best of our knowledge, only four mutations have been documented from GJB2 in pure PEODDN cases. Herein, we reported an 18-year-old female who presented with a hyperkeratotic plaque on the dorsal side of the proximal interphalangeal joint of her right ring finger as well as multiple small linear hyperkeratotic papules distributed over the lateral side of her her right index, middle and ring fingers noted since her birth. Histopathologic study revealed prominent parakeratotic cornoid lamella-like tiers at the opening of eccrine secretory ducts. Sanger sequencing focusing on the GJB2 gene revealed a germline heterozygous missense mutation, c.608T>C (p.Ile203Thr) in the blood and the epidermal tissue of the affected skin. Whole exome sequencing (WES) on the genomic DNA extracted from the lesional epidermis identified another second-hit postzygotic somatic reported missense mutation, c.263C>A (p.Ala88Glu) with low mosaic percentage of around 4% and reflecting the dilutional effect in biopsy of whole tissue and limit of detection by Sanger sequencing. In conclusion, this study presents a case of PEODDN with a complete genetic study identifying a germline mutation and a second-hit postzygotic somatic mutation; our findings strengthen the importance of second- hit somatic mutation in GJB2 as an etiology in PEODDN.