Suzanne de Bruijn

28 Chapter 1.1 light stimuli”, which indicates there are numerous proteins that play crucial roles in the sensory cells of both the retina as well as the inner ear. The majority of the proteins that are linked to this category consider proteins that have been linked to Usher syndrome (e.g. cadherin 23, myosin VIIa, and harmonin). Other biologically processes enriched for HL-associated proteins include hair cell bundle morphogenesis, cochlear ion homeostasis, extracellular matrix formation, mechanostability, and maintenance and gene regulation. 47 1. Sensory perception of mechanical stimulus or sound (GO:0050954, GO:0007605) 2. Sensory perception of light stimulus (GO:0050953) 3. Inner ear receptor stereocilium organization (GO:0060122) 4. Inner ear receptor cell development (GO:0060119) 5. Equilibrioception (GO:0050957) 6. Inner ear receptor cell differentiation (GO:0060113) 7. Inner ear morphogenesis (GO:0042472) 8. Neuromuscular process controlling balance (GO:0050885) 9. Auditory receptor cell differentiation (GO:0042491) 10. Sensory perception (GO:0007600) Figure 4. Biological processes linked to hearing loss-associated genes. A gene ontology (GO) enrichment analysis was performed to visualize biochemical processes that are significantly associated with hearing loss (HL). The top 10 of biochemical processes that show enrichment for HL-associated proteins has been indicated. The length of the colored bars represents the association strength (-log10(p-value)). GO-term enrichment analysis was performed using Enrichr 14 and based on the GO biological processes term list (2018). HL-associated genes (n=154) were extracted from the Hereditary Hearing Loss Homepage (May 2021). In diagnostic practices, genetic prescreening approaches are currently still preferred before continuing with performing exome or genome sequencing. These prescreening approaches can involve screening for pathogenic variants in the GJB2 gene only, or other candidate genes in case of a strong phenotype-genotype correlation. For instance, variants in the SLC26A4 gene are associated with recessive HL and a unilateral or bilateral enlargedvestibular aqueduct. Also, somegenetic forms of HL canbedistinguishedbased on audiogram shape. Age Related Typical Audiograms (ARTA) have been developed, in which the latest pure tone thresholds of individuals are analyzed cross-sectionally