Suzanne de Bruijn

255 Exploring the missing heritability in subjects with hearing loss and EVA groups versus the M0 group suggests that SLC26A4 defects have a prognostic value which can be strengthened in the future by the identification of the underlying genetic defects in subjects of the M0 group. In conclusion, the HL and EVA in 12 of the 28 studied subjects could be associated with SLC26A4 . In addition, we have identified genetic factors that might (partially) explain the phenotype in four additional subjects. However, we could not pinpoint the genetic defect that is present on the CEVA haplotype. The arrival of third-generation sequencing techniques, the expansion of epigenetic and transcriptomic datasets and the increasing understanding of non-coding, structural, and regulatory variants will aid in solving the missing heritability in SLC26A4 in the coming years. This is of great importance for counseling patients about the underlying cause and expected prognosis of their HL. Furthermore, as variants in SLC26A4 are a frequent cause of HL 10 , it is an interesting target for the development of a genetic therapy. 93 Although the involved molecular defect of the CEVA haplotype is still not resolved, the high prevalence of the CEVA haplotype suggests that a significant portion of monoallelic SLC26A4 cases can be associated with SLC26A4 defects by testing for the presence of this haplotype.