Connexin 26 studies in patients with sensorineural hearing loss

Objective: To determine the spectrum of connexin 26 (Cx26) mutations and th eir phenotypes in children with sensorineural hearing loss (SNHL) or mixed hearing loss (MHL). Design: Children with SNHL or MHL were prospectively tested for mutations i n the entire coding region of the Cx26 gene. Patients: Children with SNHL or MHL with no obvious etiology for the hearin g loss. Results: Between December 1, 1998, and July 1, 2000, 107 patients with SNHL or MHL from 99 families underwent Cx26 testing. Most patients were aged 1 week to 16 years (61 boys and 46 girls). Thirty (30%) of 99 probands had Cx 26 mutations: biallelic mutations were detected in 18 (9 homozygous and 9 c ompound heterozygous) and single mutations were detected in 12. Twelve prev iously reported mutations (35delG, 167delT, E47X, L90P, M34T, G12V, V37I, R 143W, V84L, V153I, V27I, and 310del14) and 3 novel mutations (E129K, T8M, a nd N206S) were found. Hearing loss in patients with biallelic Cx26 mutation s ranged from unilateral high frequency to bilateral profound. Four childre n, 2 with biallelic mutations, had temporal bone abnormalities. Conclusions: Connexin 26 mutations are common in children with SNHL, and it is likely that the homozygous and compound heterozygous mutations cause th e SNHL. However, pathogenicity is less certain where only a single Cx26 mut ation is present. Patients with biallelic Cx26 mutations had a slightly hig her incidence of milder hearing loss than ire previous studies. Children wi th SNHL or MHL should be tested for Cx26 mutations early in their evaluatio n.