Clinical And Molecular Characteristics In A Large Chinese Pedigree With Autosomal Dominant Deafness

ObjectiveTo investigate the audiological features of a large Chinese family with autosomaldominant hereditary hearing loss, and to perform a mutational analysis of candidategenes.MethodsAfter obtaining informed consent from all participants, medical and audiologicalexaminations were performed to rule out any syndromic hearing impairment, and theinheritance mode of the family was evaluated. Genomic DNA was isolated from theperipheral leukocytes of the subjects using the Puregene DNA Isolation Kits. TheDNA fragments spanning the entire coding regions of GJB2and GJB3genes, and50exons in other23cloned autosomal dominant deafness genes were PCR amplifiedusing specific primers. Each fragment was purified and subsequently analyzed bydirect sequencing.ResultsThe family had199members in7generations, in which176members in4generations were alive.54subjects, including24males and30females, were found tobe hearing-impaired. The mode of inheritance of the family was consistent with theautosomal dominant according to the pedigree. Hearing impairment was found in thesecond or third decade. Audiograms showed bilateral symmetric, progressive, andsensorineural hearing loss which started from high frequencies and quickly expendedto mid and low frequencies. We failed to detect any known deafness-associated genemutations by PCR amplification and direct sequence analysis.Conclusions Pedigree analysis suggested an autosomal dominant hereditary pattern in thisfamily. Hearing loss was bilateral symmetric, progressive and sensorineural with lateonset. The known deafness loci seem not contributing to the pathogenesis of thehearing loss in this Chinese family, which suggesting new gene(s) or mutation(s)involvement.