title: Porokeratotic eccrine nevus may be caused by somatic connexin26 mutations.
abstract: Porokeratotic eccrine ostial and dermal duct nevus, or porokeratotic eccrine nevus (PEN), is a hyperkeratotic epidermal nevus. Several cases of widespread involvement have been reported, including one in association with the keratitis-ichthyosis-deafness (KID) syndrome (OMIM #148210), a rare disorder caused by mutations in the GJB2 gene coding for the gap junction protein connexin26 (Cx26). The molecular cause is, as yet, unknown. We have noted that PEN histopathology is shared by KID. The clinical appearance of PEN can resemble that of KID syndrome. Furthermore, a recent report of cutaneous mosaicism for a GJB2 mutation associated with KID describes linear hyperkeratotic skin lesions that might be consistent with PEN. From this, we hypothesized that PEN might be caused by Cx26 mutations associated with KID or similar gap junction disorders. Thus, we analyzed the GJB2 gene in skin samples from two patients referred with generalized PEN. In both, we found GJB2 mutations in the PEN lesions but not in unaffected skin or peripheral blood. One mutation was already known to cause the KID syndrome, and the other had not been previously associated with skin symptoms. We provide extensive functional data to support its pathogenicity. We conclude that PEN may be caused by mosaic GJB2 mutations.
authors.affiliation: Department of Dermatology, Maastricht University Medical Center, Maastricht, The Netherlands. jennifer.easton@maastrichtuniversity.nl
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Easton
authors.forename: Steven
authors.initials: S
authors.lastname: Donnelly
authors.forename: Miriam A F
authors.initials: MA
authors.lastname: Kamps
authors.forename: Peter M
authors.initials: PM
authors.lastname: Steijlen
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Martin
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tadini
authors.forename: René
authors.initials: R
authors.lastname: Janssens
authors.forename: Rudolf
authors.initials: R
authors.lastname: Happle
authors.forename: Michel
authors.initials: M
authors.lastname: van Geel
authors.forename: Maurice A M
authors.initials: MA
authors.lastname: van Steensel
mesh_terms: D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D003638:Deafness / Q000235:genetics; D006801:Humans; D007057:Ichthyosis / Q000235:genetics; D007634:Keratitis / Q000235:genetics; D009154:Mutation; D009506:Nevus / Q000235:genetics* / Q000473:pathology; D017499:Porokeratosis / Q000235:genetics* / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26