Phenotypic characterization of hereditary hearing impairment linked to DFNA25.

OBJECTIVES: To clinically characterize a family with nonsyndromic sensorineural hearing loss linked to the DFNA25 gene and to assess whether mitochondrial mutations influence the penetrance of the phenotype.
DESIGN: Longitudinal clinical and basic science molecular genetic study.
SETTING: Academic medical center and molecular genetic research laboratory. PARTICIPANTS: Members of a family with dominant high-frequency sensorineural hearing loss.
INTERVENTIONS: Questionnaires, serial audiograms, and interviews correlated with molecular genetic data. MAIN OUTCOME MEASURES: Symptoms, age at onset, serial audiometric data, and the presence or absence of 4 deafness-associated mitochondrial mutations.
RESULTS: Affected individuals typically manifest a high-frequency, slowly progressive sensorineural hearing loss in the postlingual period. The mode of inheritance is autosomal dominant with age-dependent penetrance. Male affected members tended to report an earlier onset of hearing loss than female members. In those inheriting the DFNA25-associated haplotype from an affected mother, hearing loss invariably developed by the second decade of life, whereas those inheriting the DFNA25 haplotype from an affected father often maintained hearing levels comparable to those of age-matched control subjects, even into the seventh decade of life. None of 4 deafness-associated mitochondrial mutations screened (1555A>G, 7445A>G, Cins7472, and 7511T>C) were found to segregate in the family.
CONCLUSIONS: It is difficult to differentiate delayed-onset high-frequency sensorineural hearing loss inherited as a simple mendelian trait like DFNA25-associated hearing loss from that due to noise exposure or presbycusis, disorders that may also have a genetic component. An awareness of the clinical presentation of such hearing loss may help clinicians identify hearing loss attributable to genetic causes and improve care for these patients.