Clinical Profiles of DFNA11 at Diverse Stages of Development and Aging in a Large Family Identified by Linkage Analysis

Hypothesis:The phenotype of DFNA11 consists of specific features at diverse developmental and age stages.Background:Only eight mutations have been identified for autosomal dominant non-syndromic hearing loss related to MYO7A (DFNA11), and the onset and progression of DFNA11 are poorly understood.Methods:After linkage analysis and following Sanger sequencing in a family suspected to have autosomal dominant hereditary hearing loss, we analyzed the audiometric and vestibular functions and their long-term changes in the subjects carrying the variant.Results:A reported variant of uncertain significance, NP_000251.3:p.Arg853His, in MYO7A was detected and cosegregation data of this large family provided evidence that the variant was likely pathogenic for DFNA11. Family members with the variant had no other symptoms associated with hearing loss and were confirmed to have autosomal dominant non-syndromic sensorineural hearing loss. Audiograms tended to show gently sloping configuration in childhood and flat configuration after the age of 30 years. Hearing loss at high frequencies progressed slowly, while hearing at low frequencies started to deteriorate later but progressed more rapidly. Some subjects showed partly abnormal results in the distortion products of otoacoustic emissions before the elevation of hearing thresholds. Vestibular function was within the normal range in all the subjects tested.Conclusion:We revealed that hearing loss at high frequencies was mainly noted in early developmental stages and that thresholds increased more rapidly in the low frequency range, resulting in changes in audiometric configuration. Deterioration of distortion product otoacoustic emissions (DPOAE) before the elevation of hearing thresholds was considered as a clinical feature of DFNA11.