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Precise auditory phenotyping is crucial to link genetic variants with their functional consequences and vice versa. While known genetic causes of hearing loss are mostly associated with severe hearing loss typically associated with Cochlear Implant indication, recent studies even consider mild-to-moderate hearing impairment connected, e.g. to hearing aid indication – primarily due to better and less expensive genotyping.

This talk will review our current work in the PRESAGE project (Institut d’Audition, Paris, and Universität Oldenburg) and will highlight the preparatory work for a common Lower Saxony cohort on hearing health with the partner universities Göttingen, MHHannover, and Oldenburg.

In PRESAGE, we characterize untimely age-related hearing loss (uARHL, aged ≥40 years) and age-matched controls with normal hearing using a comprehensive test battery, including pure-tone audiometry, speech recognition in quiet and noise, suprathreshold psychoacoustic measures, loudness scaling, electrophysiology, and vestibular assessments. This phenotypic characterization is presented by Warzybok et al. at the current congress. Parallel genetic analyses, performed in collaboration with the Institut de l’Audition (Paris), indicates a high prevalence (29% from N=141) of genetic abnormalities related to hearing with a high heterogeneity and mostly monogenetic mutations. Examples of identified genes are MYO3A (4 cases), MYO VIIA (3 cases), and GJB2 (N=2), all known to cause hair cell damage.

To proceed, the number of patients for an initial, “flat phenotyping and genotyping” approach should be dramatically extended, e.g. by using the virtual hearing clinic (VHC) for self-controlled phenotyping and sputum swipes for a genotyping. On the other hand, a “deep phenotyping and genotyping” approach is needed to align the clinical auditory phenotyping approaches across audiological diagnostic units and to characterize more auditory genes with appropriate animal models. This will be part of a Lower Saxony consorted action where some preliminary work will be reported on.