Congenital hearing loss

Hearing loss is the most common sensory deficit in humans, affecting 1 in 500 newborns. Due to its genetic heterogeneity, comprehensive diagnostic testing has not previously been completed in a large multiethnic cohort. To determine the aggregate contribution inheritance makes to non-syndromic hearing loss, we performed comprehensive clinical genetic testing with targeted genomic enrichment and massively parallel sequencing on 1119 sequentially accrued patients. No patient was excluded based on phenotype, inheritance or previous testing. Testing resulted in identification of the underlying genetic cause for hearing loss in 440 patients (39 %). Pathogenic variants were found in 49 genes and included missense variants (49 %), large copy number changes (18 %), small insertions and deletions (18 %), nonsense variants (8 %), splice-site alterations (6 %), and promoter variants (<1 %). The diagnostic rate varied considerably based on phenotype and was highest for patients with a positive family history of hearing loss or when the loss was congenital and symmetric. The spectrum of implicated genes showed wide ethnic variability. These findings support the more efficient utilization of medical resources through the development of evidence-based algorithms for the diagnosis of hearing loss. Electronic supplementary material The online version of this article (doi:10.1007/s00439-016-1648-8) contains supplementary material, which is available to authorized users.

Objective: Age-related hearing loss is an increasingly important public health problem affecting approximately 40% of 55–74 year olds. The primary clinical management intervention for people with hearing loss is hearing aids, however, the majority (80%) of adults aged 55–74 years who would benefit from a hearing aid, do not use them. Furthermore, many people given a hearing aid do not wear it. The aim was to collate the available evidence as to the potential reasons for non-use of hearing aids among people who have been fitted with at least one. Design: Data were gathered via the use of a scoping study. Study sample: A comprehensive search strategy identified 10 articles reporting reasons for non-use of hearing aids. Results: A number of reasons were given, including hearing aid value, fit and comfort and maintenance of the hearing aid, attitude, device factors, financial reasons, psycho-social/situational factors, healthcare professionals attitudes, ear problems, and appearance. Conclusions: The most important issues were around hearing aid value, i.e. the hearing aid not providing enough benefit, and comfort related to wearing the hearing aid. Identifying factors that affect hearing aid usage are necessary for devising appropriate rehabilitation strategies to ensure greater use of hearing aids.

The auditory inner hair cell (IHC) ribbon synapse operates with an exceptional temporal precision and maintains a high level of neurotransmitter release. However, the molecular mechanisms underlying IHC synaptic exocytosis are largely unknown. We studied otoferlin, a predicted C2-domain transmembrane protein, which is defective in a recessive form of human deafness. We show that otoferlin expression in the hair cells correlates with afferent synaptogenesis and find that otoferlin localizes to ribbon-associated synaptic vesicles. Otoferlin binds Ca(2+) and displays Ca(2+)-dependent interactions with the SNARE proteins syntaxin1 and SNAP25. Otoferlin deficient mice (Otof(-/-)) are profoundly deaf. Exocytosis in Otof(-/-) IHCs is almost completely abolished, despite normal ribbon synapse morphogenesis and Ca(2+) current. Thus, otoferlin is essential for a late step of synaptic vesicle exocytosis and may act as the major Ca(2+) sensor triggering membrane fusion at the IHC ribbon synapse.