Functional Analysis of a Novel Connexin30 Mutation in a Large Family with Hearing Loss, Pesplanus, Ichthyosis, Cutaneous Nodules, and Keratoderma

Summary Mutations in the gap‐junction gene Cx30 (Connexin30, GJB6) are a known cause of hearing loss. Here, we report our findings on a large multigeneration family in which severe to profound sensorineural hearing impairment is associated with a variety of skin‐related anomalies. Genome‐wide analysis of the family showed that the locus maps to chromosome region 13ptel‐q12.1 and that a novel mutation, p.N54K, in Cx30, cosegregates with the phenotype. Unlike wild‐type Cx30, p.N54K Cx30 is predominantly localized in the cytoplasm and does not permit transfer of neurobiotin, suggesting improper cellular localization and abolishment of gap‐junction activity.