GJB2 and GJB6 mutations in children with congenital cytomegalovirus infection.

Congenital cytomegalovirus (CMV) infection is a leading cause of sensorineural hearing loss (SNHL) in children. Whether connexin mutations are factors in the development of CMV-related hearing loss has not been explored. We examined gap junction protein beta-2 (GJB2) and gap junction protein beta-6 (GJB6) mutations in 149 children with congenital CMV infection and 380 uninfected neonates. Mutations in GJB2 and GJB6 were assessed by nucleotide sequencing and polymerase chain reaction (PCR) methods, respectively. The study population was predominantly African American, and 4.3% of the subjects were carriers of a connexin 26 mutation. The overall frequency of GJB2 mutations was significantly higher in the group of children with CMV infection and hearing loss (21%) compared with those with CMV infection and normal hearing (3%, p = 0.017) and the group of uninfected newborns (3.9%, p = 0.016). Eight previously reported mutations (M34T, V27I, R127H, F83L, R143W, V37I, V84L, G160S), and four novel mutations (V167M, G4D, A40T, and R160Q) were detected. None of the study children had the 342-kb deletion (delGJB6-D13S1830) in GJB6, which suggests that this mutation does not play a role in hereditary deafness in the African American population. Although GJB2 mutations were detected in children with and without CMV-related hearing loss, those with hearing loss had a higher frequency of GJB2 mutations.