GJB2

GJB2, also known as connexin 26, is a human gene that encodes a gap junction protein of the connexin family. The connexin 26 protein forms hexameric channels that assemble into gap junctions, enabling direct intercellular communication. In the inner ear, connexin 26 is expressed mainly in supporting cells of the organ of Corti and plays a role in potassium ion recycling and cellular signaling essential for normal auditory function.

Genetic variants in GJB2 are a leading cause of hereditary non-syndromic sensorineural hearing loss. Most pathogenic variants follow an autosomal recessive inheritance pattern (DFNB1A), although rare dominant mutations are associated with syndromic conditions such as keratitis-ichthyosis-deafness (KID) syndrome. The spectrum includes common founder mutations as well as many rare variants; more than a hundred disease-causing changes have been described.

Common pathogenic variants include 35delG (well documented in European populations), 167delT (found among Ashkenazi Jewish individuals), and 235delC (noted in East Asian populations). The exact prevalence of GJB2-related hearing loss varies by ethnicity, but variants in this gene account for a substantial proportion of severe-to-profound congenital hearing loss worldwide.

Diagnosis and management typically involve genetic testing for GJB2 variants in individuals with congenital or early-onset hearing loss, often as part of a broader deafness gene panel or exome sequencing. Management emphasizes appropriate amplification, cochlear implantation when indicated, and genetic counseling for families. In cases involving GJB2 plus GJB6 deletions, testing for both genes is considered.