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Margaret A. Kenna, MD; Bai-Lin Wu, PhD; Douglas A. Cotanche, PhD; Bruce R. Korf, MD, PhD; Heidi L. Rehm, PhD

Arch Otolaryngol Head Neck Surg. 2001;127:1037-1042.

Objective  To determine the spectrum of connexin 26 (Cx26) mutations and their phenotypes in children with sensorineural hearing loss (SNHL) or mixed hearing loss (MHL).

Design  Children with SNHL or MHL were prospectively tested for mutations in the entire coding region of the Cx26 gene.

Patients  Children with SNHL or MHL with no obvious etiology for the hearing 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 Cx26 mutations: biallelic mutations were detected in 18 (9 homozygous and 9 compound heterozygous) and single mutations were detected in 12. Twelve previously reported mutations (35delG, 167delT, E47X, L90P, M34T, G12V, V37I, R143W, V84L, V153I, V27I, and 310del14) and 3 novel mutations (E129K, T8M, and N206S) were found. Hearing loss in patients with biallelic Cx26 mutations ranged from unilateral high frequency to bilateral profound. Four children, 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 the SNHL. However, pathogenicity is less certain when only a single Cx26 mutation is present. Patients with biallelic Cx26 mutations had a slightly higher incidence of milder hearing loss than in previous studies. Children with SNHL or MHL should be tested for Cx26 mutations early in their evaluation.

From the Department of Otology and Laryngology, Harvard Medical School, Boston, Mass (Drs Kenna and Cotanche); the Department of Otolaryngology and Communication Disorders (Drs Kenna and Cotanche), the Genetics Diagnostic Laboratory and the Department of Laboratory Medicine (Dr Wu), and the Laboratory of Cellular and Molecular Hearing Research (Dr Cotanche), Children's Hospital Boston; and Partner's Center for Human Genetics (Dr Korf) and the Department of Neurobiology (Dr Rehm), Massachusetts General Hospital, Harvard Medical School, Boston.

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