Specific loss of connexin 26 expression in ductal sweat gland epithelium associated with the deletion mutation del(GJB6-D13S1830)

A whole array of cutaneous syndromes is associated with distinct dominant mutations in GJB2 encoding the gap junction protein connexin 26 (Cx26), including Vohwinkel's syndrome and keratitis-ichthyosis-deafness syndrome. In contrast, recessive GJB2 mutations occur in a large proportion of individuals with hearing loss but no obvious dermatological phenotype. Recently, a large deletion of similar to 342 kb, encompassing the coding region of GJB6 encoding Cx30, but not affecting GJB2, was shown to be associated with hearing loss. From analysis of patient skin, we provide immunohistochemical and bioinformatic data to show that the expression of Cx26 is affected by del(GJB6-D13S1830) in a cell-type-specific manner within the sweat gland. This putative regulatory element of Cx26 expression may be a key factor related to the severe or profound deafness associated with del(GJB6-D13S1830).